Drug Test for Employees - provided by CNN Money Small Business BlogDrug Tests for Employees

Your Answers
AFrom danny, las vegas nevada

wow! out of the whole country there are people that have everything against marijuana even if they do not use it or have relations with. Then there are people like the simon who get it. let us be.
Posted By danny, las vegas nevada : November 17, 2009 3:44 pm
Comment
AFrom Pasquale Santoro Manhattan N.Y.

Drug testing is a complete violation of human rights, an invasion of privacy, degrading and undignified. The interviewing process is degrading enough. You are made to feel small even though your interest in working for them may be genuine. Your made out to feel you need them more then they need you. To throw a drug test on top of it confirms there position.' We own you". Your relationship with your employer should stop when you hit that punch out clock. If they are not allowed to dig in your pockets or show up at your home and check your closets and draws then I can't see how they can force you to submit to a urine test or D.N.A. test. As an equal opportunity employer I can't see why they would want to. There are exception though. Working in law enforcement as well as being a politician. In theses area's your job is 24/7. How you carry yourself here is under constant scrutiny as a public servant of the people on and off the clock. Also if there is a noticeable problem with an employee I believe its the right of the company to enforce a drug test, but only then. Walking through the door and getting hired should be based on your qualifications and the presentation of ones self. In these area's you should be treated fair and with trust just the way an employer should never lie to you about your salary or quality of a job being applied for. Employers must understand they do not own you and that you should not be judged on your skin color,race,religion,creed,personal beliefs,personal life style as well as your urine and especially your D.N.A. as it is the social security number or code to your heritage past and future, your traits and geography, your brain power, your complete total make up, even diseases that have been past along from generation to generation, sorry that belongs to you and you alone and no one and I mean no one has the right to force you to give that up because you showed an interest in providing services to a specific employer. Hands down!

P.S. The companies that provide these testings have no interest in human rights but they do have an interest in the almighty dollar. Keep that in mind.
Posted By Pasquale Santoro Manhattan N.Y. : October 21, 2009 11:07 am
Comment
AFrom Anon

The fact of the matter is, the only drugs that are fat soluble (the ones most likely to be caught by a urine test) are nicotine, marijuana, and some prescription painkillers and anti depressants(because pharmaceutical companies have made them that way for this explicit purpose). A person who uses water soluble drugs, such as cocaine, heroin, barbituates, speed, etc (pretty much every other drug you can imagine) is able to pass a drug test solely by drinking a bunch of water and working out for an hour(like vitamins and other minerals these drugs are water soluble).
Not to mention these test are not accurate assessments of alcohol, prescription drug use, or over the counter drug use, which also have a huge effect on worker productivity. People who take sleep aids like tylenol pm, and other over the counter medicines, are just as likely to be causing those accidents, as a person who smokes pot.
Also, because a lot of companies don't pay for the more expensive gc/ms tests, they do a more standard dot test, they aren't going to catch drug users who know their way around the system. So in that effect, they are totally inefficient.
I am also amazed at these figures of 7,0004 per user. Where exactly did you get that study, and what is it sourced from (for my own edification)? Drug statistics like that have a tendancy to be completely false (seeing as to make a study on a banned substance you need to jump through an unbelievable amount of red tape). I assume that most of these figures come from "after the fact" drug testing, where people who already screwed up get drug tested and then the blame falls squarely on the drugs not the ineptitude of the person.
The fact of the matter is, most companies don't care whether you are a drug user or not. All they care about is your productivity, a drug free workplace, with entrance testing, is usually a "don't ask don't tell unless I want to fire you because you screwed up" workplace. If your most productive person smokes pot on his time off, you think that he should be fired. And if so, if all your productive workers would fail a drug tet, would you make them take it. few companies face this problem down, as a matter of fact, I've had experiences with companies who realized how many people of theirs smoked, and realized that it would be far LESS profitable for them to do random drug tests. How many dollars per user does being an idiot cost a company a year anyway? I'd wager far more than drug users.
Posted By Anon : January 15, 2009 11:07 am
Comment
AFrom Larsen Petty

Terry Box quoted;"The national average estimate for the cost of substance abuse to a company per user is $7,000 in lost productivity, accidents, absenteeism and replacing fired and suspended employees."Unquote I know many people who work beyond thier means and are stoners so to say.
What about the average person who doesnt miss work, & provides great quality in work such as exceeding production levels and maintains good work attitude? Don't get me wrong, Im opposed for the person who wants to come in to a work place stoned or drunk. I don't think that a person should be persecuted for what he/she does outside the workplace,as long as it's not a danger to anyone and it doesnt take control of life. Why should it be posed as a threat if you get sent down for a random test,it comes back positive and it's only because of what you do recreationally away from the work place after hours???
Posted By Larsen Petty : December 11, 2008 5:51 pm
Comment
AFrom Mr. T, bismarck,nd

100% agree as with probably 60% of america he have little rights left and everything we do is critisized. i should not be judged by the quality of my piss but buy the quality of my caracter, cause i may smoke a little harmless pot on sat. doesnt have a thing to do with what happens on wed.
Posted By Mr. T, bismarck,nd : October 27, 2008 12:00 am
Comment
AFrom krack hore

It all depend on the type of job that is being performed. How much will it effect a writer if he goes to work stoned compared to a school right.
Posted By krack hore : October 19, 2008 6:58 am
Comment
AFrom Ivan Vodenlic

Invasion of privacy? what? I hire, I own the company, and employees are compensated well. What you do on your own time is your business but don't tell me how to run my business. Pre employment requires passing a drug test. Don't like it then hit the road. Oh you say it has no impact on your work, well I know a few former employees looking for jobs so if you need you kids watched I'd be happy to help both of you out and send them your way. Have a nice day.
Posted By Ivan Vodenlic : August 25, 2008 5:19 pm
Comment
AFrom Terry Box, Columbus, Ohio

Every employer should test for drug use in the workplace. Why?

The national average estimate for the cost of substance abuse to a company per user is $7,000 in lost productivity, accidents, absenteeism and replacing fired and suspended employees.
Use the following formula to estimate the cost of employee substance abuse in your business:
1. Estimate the percentage of your total number of employees that use drugs. The national average is 17 percent.
2. Multiply the number of employees you have by this percentage.
3. Multiply that by the national average cost per substance abuser ($7,000).
4. The result is the annual cost of substance abuse within your company.

National Chamber of Commerce quote.

We use a company at http://www.1mdllc.com.
Posted By Terry Box, Columbus, Ohio : August 21, 2008 3:29 pm
Comment
AFrom Darcy, Amsterdam NY

I think that drug testing in the workplace is a violation of a person's right to privacy. I believe that the best plan of action is to use "probable cause". If an employee comes to work with obvious signs of intoxication or other drug use, then the workplace should have to right request a drug test. Otherwise, what a person does on their own time should not be of anyone elses concern.
Posted By Darcy, Amsterdam NY : July 14, 2008 2:49 pm
Comment
AFrom Chris, Belfast, Ireland

I dont own a business, though I would just like to point out that, according to Kevin (below, apparently the "President and Founder of Cal-Test Drug Testing Services", although I'd beg to differ as he has made enough spelling mistakes to prove he may be on drugs himself!), you can actually get fired for not taking drugs. Especially if the tests are as innaccurate as he claims. Taking drugs doesn't make you less of a person/employee, but abusing them can.
Posted By Chris, Belfast, Ireland : May 8, 2008 1:38 pm
Comment
AFrom Michael

if you dont do drugs you wont get fired
Posted By Michael : April 12, 2008 9:19 pm
Comment
AFrom M Rose. Portland, OR

What's missing here are examples of very successful companies that don't drug test their employees upon hiring.

For example?

Microsoft and Nike.

These are successful companies by anyone's standards. Why don't they drug test? Certainly the drug testing companies have pitched their product to them.

The mainstream media has missed this very salient point in the debate over drug testing in the workplace.
Posted By M Rose. Portland, OR : January 29, 2008 11:52 am
Comment
AFrom Simon Peter Alciere, Greenfield, Massachusetts

If one of my employees smokes marijuana on the weekend, or while on vacation in Mexico, I'm supposed to fire them? That's the premise of the drug testers. Ridiculous! Is there no such thing as respect for privacy and personal responsibility?
Alcohol, cold remedies, and other "legal" drugs, are not detected by these tests. Yet they cause thousands of accidents, injuries, deaths and liability. I guess we're not worried about drinking on the job, as long as we get rid of all those "bad" people.
Posted By Simon Peter Alciere, Greenfield, Massachusetts : November 26, 2007 8:35 pm
Comment
AFrom Jacob, Santa Barbara, CA

You know the very best of your employees tend to do drugs from time to time. The drugs are not the cause of bad things, abuse is. I am not sure if you ever done drugs with the owner of a company who screens thier employees? I have…and its not right.
Posted By Jacob, Santa Barbara, CA : November 16, 2007 3:04 am
Comment
AFrom Anonymous

Drug testing in the work place is hypocrisy. I worked as an IT consultant for a telephone firm and was treated more like a factory worker. Having to carry cups of pee through the work place every few months was degrading enough. I have two BA's and spent my life working as a professional only to be treated like a crack smoking junkie.
The policy states that all employees should be random tested…yea right. Management does not get tested. Friends and relatives don’t get tested. Even a secretary whose husband is a known meth dealer does not get tested.
I have no problems with drug testing. I do with hypocrisy of management to discriminate on who gets tested.
Posted By Anonymous : November 7, 2007 5:28 pm
Comment
AFrom Kevin Odenbaugh CAL-TEST, Inc.

I'm the President and Founder of Cal-Test Drug Testing Services (www.caltest.cc). We have been providing urine, hair, fingernail, saliva and breath testing for over 16 years, to both public and private employers.

After reading your article I was compelled to tell you the real story about these inferour "Instnat" testing devices.

The down side with POC-T (Point of Collection Tests), such as the device you covered, is the lack of specificity (accuracy at precise levels). These "Instant" tests have a magin of error of, AT BEST, 25% at the cut-off.

For example, if the Donor used illegal drugs two days ago and currently has 1,250 ng/ml (A POSITIVE LAB TEST), the "Instant" may miss it due to the instant tests poor performance. Now the employer has hired a known drug abuser. This will cause additonal liability for the hiring Company due to neglagent hiring practices…the employer dio not use the best test avaiable and failed to research the instant tesst true ability to accuratley idenify drug absuers before hiring them or before placing them in a hazardous work environments. This is why the Federal Department of Transportation restricts the use of these tests!

Additonally, these Instant test devises are EASILY BEATEN by drug abusers. Most of these tests do not test for adulatration or diaredic products that drug abusers commonley use to "Dilute" or defeat the urine testing process. LAB BASED urine drug tests do idenitfy these tactics and the employer is well protected.

Finally, these POC-T tests are EASILY misused by employers. For example, if the instant test shows a "Pending", "Inconclusive", "Non-Negative" or "Suspect Positive" result, the hasty employer will ASSUME that this reading is a true "Positive" for illegal drug use WITHOUT sending the sample to a REAL Forensic Lab for GC/MS Confirmation and Medical Review Officer (MRO) review. This temptation will falsly accuse applicant/employee as being illegal drug users, when indeed they are NOT!

Simple over the counter cold and flu medications and some foods can trigger a "Positive" reading on these instant tests and MUST be confirmed via GC/MS and those results reviewed by a certifed Medical Review Officer PRIOR to taking any negative action against an employee/applicant.

The famous saying "if it sounds to good to be true…it probabley is". In the case of instant test devices it is NOT worth the risk!

Kevin Odenbaugh, C-SAPA/CPC-T/MRO-A
President
Posted By Kevin Odenbaugh CAL-TEST, Inc. : November 2, 2007 1:19 pm
Comment
AFrom Kevin Odenbaugh CAL-TEST, Inc.

I'm the President and Founder of Cal-Test Drug Testing Services (www.caltest.cc). We have been providing urine, hair, fingernail, saliva and breath testing for over 16 years, to both public and private employers.

After reading your article I was compelled to tell you the real story about these inferour "Instnat" testing devices.

The down side with POC-T (Point of Collection Tests), such as the device you covered, is the lack of specificity (accuracy at precise levels). These "Instant" tests have a magin of error of, AT BEST, 25% at the cut-off.

For example, if the Donor used illegal drugs two days ago and currently has 1,250 ng/ml (A POSITIVE LAB TEST), the "Instant" may miss it due to the instant tests poor performance. Now the employer has hired a known drug abuser. This will cause additonal liability for the hiring Company due to neglagent hiring practices…the employer dio not use the best test avaiable and failed to research the instant tesst true ability to accuratley idenify drug absuers before hiring them or before placing them in a hazardous work environments. This is why the Federal Department of Transportation restricts the use of these tests!

Additonally, these Instant test devises are EASILY BEATEN by drug abusers. Most of these tests do not test for adulatration or diaredic products that drug abusers commonley use to "Dilute" or defeat the urine testing process. LAB BASED urine drug tests do idenitfy these tactics and the employer is well protected.

Finally, these POC-T tests are EASILY misused by employers. For example, if the instant test shows a "Pending", "Inconclusive", "Non-Negative" or "Suspect Positive" result, the hasty employer will ASSUME that this reading is a true "Positive" for illegal drug use WITHOUT sending the sample to a REAL Forensic Lab for GC/MS Confirmation and Medical Review Officer (MRO) review. This temptation will falsly accuse applicant/employee as being illegal drug users, when indeed they are NOT!

Simple over the counter cold and flu medications and some foods can trigger a "Positive" reading on these instant tests and MUST be confirmed via GC/MS and those results reviewed by a certifed Medical Review Officer PRIOR to taking any negative action against an employee/applicant.

The famous saying "if it sounds to good to be true…it probabley is". In the case of instant test devices it is NOT worth the risk!

Kevin Odenbaugh, C-SAPA/CPC-T/MRO-A
President
Posted By Kevin Odenbaugh CAL-TEST, Inc. : November 2, 2007 1:19 pm
Comment
AFrom William Schraeder

Great, nice to know you are looking out for us, Jason. In your police state, do we get free food and shelter too? I mean, after all, we all want a big brother looking out for us that tells us what we can and cannot do, and drug testing is a natural extension to that. While I am not a drug user, it is comforting to know that there are so many caring people out there who know better than I what I should and should not be doing. In fact, can anyone chime in here to tell me whether I should be reading CNNFn at 6:30am in the morning….certainly there are other things I should be doing?
Posted By William Schraeder : October 3, 2007 6:59 am
Comment
AFrom Jason, The Colony, TX

Yes – the best time to do it – prevent the problem by avoiding it right off the bat. We have a drug free workplace policy and we let them know up front with a drug test.
Posted By Jason, The Colony, TX : September 21, 2007 2:57 pm
Comment

Approximate values for detection periods
Substance Urine Hair Blood / Oral Fluid
Alcohol 6–24 hours [3] up to 90 days 12–24 hours
Amphetamines (except meth) 1 to 3 days[4] up to 90 days 12 hours
Methamphetamine 3 to 5 days[5] up to 90 days 1–3 days[5]
MDMA (Ecstasy) 24 hrs up to 90 days 25 hours
Barbiturates (except phenobarbital) 1 day up to 90 days 1 to 2 days
Phenobarbital 2 to 3 weeks[6] up to 90 days 4 to 7 days
Benzodiazepines Therapeutic use: up to 7 days. Chronic use (over one year): 4 to 6 weeks up to 90 days 6 to 48 hours
Cannabis 3 to 7 days, up to >30 days after heavy use and/or in users with high body fat [7] up to 90 days [7] Up to 24 hours
Cocaine 2 to 5 days with exceptions for certain kidney disorders up to 90 days 2 to 5 days
Codeine 2 to 3 days
Cotinine (a break-down product of nicotine) 2 to 4 days up to 90 days 2 to 4 days
Morphine 2 to 4 days up to 90 days 1 – 3 days
Heroin 3 to 4 days[8] up to 90 days 1– 2 days
LSD 24 to 72 hours (however tests for LSD are very uncommon) up to 3 days[citation needed] 0 to 3 hours
Methadone 3 days up to 97 days 24 hours
PCP 3 to 7 days for single use; up to 30 days in chronic users[9] up to 90 days 1 to 3 days[9]

From HairAlcoholTesting.com

The detection of illegal drugs has been an established procedure in forensic toxicology since the mid-1990s. Once ingested, opiates, cocaine, cannabinoides and amphetamines are metabolized in the body and their breakdown products enter permanently into the hair root from where they are deposited permanently in the hair in characteristic relationships parent substance/metabolite.

As hair grows from the root (at approximately 1 cm per month), these deposits are delayed to a certain extent, therefore, they can not be detected until the hair grows out a bit (2-4 weeks). The distance from the scalp of the hair portion containing drugs allows us to estimate the approximate time of drug consumption. The deposited substances are relatively stable in the face of external influences such as hair treatments, cosmetics and sunlight. Due to the way in which drugs are deposited in the hair, hair analysis provides us with a detailed view of drug consumption over the past weeks or months. Consumption on a day-to-day basis can be detected by analyzing blood and urine samples.

Trace amounts of ethanol from the environment are present in all hair including in the hair of teetotalers. Simply being in a pub or laboratory is enough for traces of ethanol to find their way into the hair.

In contrast to other drugs consumed, alcohol is not deposited directly in the hair. For this reason the investigation procedure looks for direct products of ethanol metabolism. The main part of alcohol is oxidized in the human body. This means it is released as water and carbon dioxide. One part of the alcohol reacts with fatty acids to produce esters. The sum of the concentrations of four of these fatty acid ethyl esters (FAEEs: ethyl myristate, ethyl palmitate, ethyl oleate and ethyl stearate) are used as indicators of the alcohol consumption. The amounts found in hair are measured in nanograms (one nanogram equals only one billionth of a gram), however with the benefit of modern technology, it is possible to detect such small amounts.

In the mass spectrometer the substances are fired with an electronic beam. Every molecule decomposes into specific fragments. It is possible to determine which substance is present on basis of its molecular weight.

However there is one major difference between most drugs and alcohol metabolites (FAEE) in the way in which they enter into the hair: on the one hand like other drugs FAEEs enter into the hair via the ceratinocytes, the cells responsible for hair growth. These cells form the hair in the root and then grow through the skin surface taking any substances with them. On the other hand the sebaceous glands produce FAEEs in the scalp and these migrate together with the sebum along the hair shaft (Auwarter et al., 2001, Pragst et al., 2004). So these glands lubricate not only the part of the hair that is just growing at 0.3 millimeters per day on the skin surface, but also the more mature hair growth, providing it with a protective layer of fat.


ig 1: Possible ways of incorporation of FAEEs into hair (based on Auwarter, 2006).

This means the glands supply the whole length of hair with sebum, which in turn carries FAEEs into the hair, resulting in an accumulative increase of FAEEs from proximal to distal hair sections, see next figure (Auwarter et al., 2001).

This phenomenon has one important consequence: whilst most other drugs are mainly stored in the hair via the root alone, allowing toxicologists to establish time-resolved patterns of consumption according to the length of hair provided, this is not possible with alcohol (FAEEs) with respect to previous drinking and abstinence. This would only be possible using alcohol markers which enter the hair solely through the hair root, but these have not yet been discovered.

However there exists a significant correlation between the intensity of the alcohol intake and the concentrations of the FAEEs in hair. Results between 0.05 and 30 ng/mg were found in hair (Pragst et al., 2006).


Fig. 2: Profile of FAEE concentrations (based on Pragst, 2004).

Case 1 is a strictly abstinent person. Case 2 is a social drinker. Case 3 is a patient in alcohol rehabilitation (self-reporting 60 grams ethanol per day for at least 6 months). The increase in FAEE concentrations from proximal to distal sections up to a length of 5-10 cm found in most cases could be explained by the sebum deposition route. The hair is continuously bathed by sebum, and this leads to an accumulation of the concentrations with increasing age, i.e., distance of hair from skin.

As a consequence of the increasing FAEE concentrations from proximal to distal it is preferable to always analyze, if possible, a standard length of hair. For example analysis of a 1cm hair sample taken close to the scalp will give a much lower result than the analysis of a 6 cm long sample also taken close to the scalp from the same person. For this reason we standardly use the proximal 0-6 cm segment of head hair in exactly the same procedure. For samples analyzed under these standard conditions the cutoff level is set at 1.0 ng/mg. The same holds true for body hair of any length (length is genetically determined, body hair grows more slowly and has different growth cycles, etc.). However for shorter head hair the analysis changes (e.g.: for only 3 cm we reduce the cut off level to 0.5 ng/mg). The closer the conditions (i.e. hair length) are to the standard procedure, the more certain we can be of the accuracy of the result.

A 6 cm long hair sample can be used to look back over 6 to 12 months (this is commonly used in Germany to test drivers). If head hair is not available or is too short (minimum: 2 cm) underarm, chest, leg and pubic hair may be analyzed. Body hair gives us a picture going back up to twelve months.

APPLICATION

Legal Sector

A child has just been taken away by social services due to a report that the child's parents are taking cocaine.

Within seven days, the parents applied for legal counsel to assist them in getting the child back into its regular home. Upon making an application to the court by the parent's solicitors, the legal counsel representing the child (now in care) requests for both parents to undergo hair drug testing. This is sometimes called a "tricho test" (the word derives from "trichology", meaning the study of the hair and scalp).

Upon the application, the court made an order to complete the test before the next hearing. The test was conducted on both parents over a three-month period that demonstrated both mother and father had abused cocaine in month three (60-90 days) and the results for months two (30-60 days) and month one (0-30 days) were negative. This supported the statements of both parents that their usage had decreased. Note: hair drug testing allows one to look at patterns of abuse so one can effectively judge if an individual has long-term drug dependency. Based on this, the right choices can be made for the benefit of the child.

Corporate Sector

An individual in an existing job is suspended as the company has a zero-tolerance policy against drugs.

She was asked to do a urine test (common practice in most organisations) and the results for this test demonstrated that she was suspected of using cannabis. Further investigation of the individual's medical records showed that she was having regular massages for a back injury and it was further noted that the masseur was using hemp oil. The company felt that it was necessary that considerable efforts were made to ensure that the individual was not using the illegal substance (cannabis) and sought to have a hair drug test over the last 12 months. The test results were negative for the whole period demonstrating clearly that the individual did not have any pattern of drug abuse. This corroberated and made stronger the evidence presented by the employee. Note: hair drug testing can help employers with responsibility to accurately identify whether drugs were ingested illegally or previous results from other methods were reporting false positives.

Schools

Urine testing (traditional method in random drug testing in schools) is known to be invasive, embarrassing and generates false positives.

This was identified in a recent case where a school had a parent protesting the innocence of her sons' drug test. The son assured his parents that he did not ingest any of the drugs he was accused of taking. The first step in the parents' process to prove innocence was a hair drug test to clearly show that no substance was found in the child's body in the last three months. This particular hair drug test was run at limits of detection, looking at any substances detected in the body. When this was presented to the school, the school remained supportive over their original finding in the urine test. The parents wrote to the media which raised attention to the urine test conducted and forced the school to have the testing kit itself analysed by an independant third party. It was discovered that the urine kit was faulty. If the school had chosen to use hair drug testing in the first instance, the accurate identification of possible substance abuse would have taken place in the first instance with no room for false positives.

More information can be found by visiting: TriMegaLabs

This is an alphabetical list of known laboratories that conduct Hair Follicle Drug Testing:


American Toxicology



Omega Laboratories


Pshycamedics



Quest Diagnostics


Trimega Labs


If we have omitted any laboratories that conduct hair follicle drug testing please let us know by commenting to this post.

DRUG TESTING ADVISORY BOARD
OPEN SESSION

March 7, 2006
Agenda Item: Welcome/Opening Remarks
MR. STEPHENSON (Chair): I would like to open the Drug Testing Advisory Board
meeting. We ask that the people who join us sign in at the back and let us know if you
want to make a public comment.
The HHS Mandatory Guidelines have been delivered to the Office of
Management and Budget (OMB) and they have been distributed to Federal agencies for
secondary review and additional opportunities for comments. We know that several of
the large Departments have received them, have processed them, and it is our belief have
returned them to Office of Management and Budget. I happened to have an opportunity
to meet with the OMB examiner about two weeks ago and it was acknowledged that they
are there, so we expect to hear something back and we will go the next step with
whatever is necessary from that point on.
In the scope of things, this is an extremely good sign and it is one that
pushes us towards an end game process, so it is not a done deal yet, we are not all
finished, I still cannot tell you exactly what is going to be in the final Guidelines but we
are much further along and the process is still working in the way that it was intended to
work.
There is a display that you all should take a look at when you get a chance
and there is some interesting information that puts a picture to what it is we have been
dealing with in the world of adulterants and substitutions and so on, at least in urine, and
gives you a hint of what is already being marketed for hair and oral fluid. The display
boards list a number of products, these were initially assembled for the Congressional
testimony that we provided last May. It has been continued to be updated since then, it
has been borrowed by some other Federal agencies to use in some of their presentations,
it is being used currently.
MR. MCCUNE (NRC): The HHS personnel at SAMHSA were gracious enough to let
me borrow the board for an NRC office display, the Office of Nuclear Security and
Incident Response had a show and tell day where they showed the rest of the organization
and the public what we did and we displayed the board there.
MR. STEPHENSON: The interesting thing was that sales went up 300 percent on most
of these products after that, I do not know if it has any relationship but I hope that doesn’t
happen today. But the point being that this is a very interesting part of the process and it
ties into what we are going to be doing today in talking about some of our PT samples
and the processes that we are dealing with alternative specimens, some of the things that
you are going to hear about today. They are all related and it seems like we have the
attention of the folks that are out there in the regulatory and the law-making part of this
business and some of the enforcement arena, so we can only hope that that is a continued
interest that will get some results in the not to distant future.
I needed to open the door literally and figuratively and indicate that in the
aftermath of Katrina last year we had lost access to one of our labs, a Kroll Lab, in
Gretna, part of New Orleans complex area, and not only were the staff displaced and their
homes flooded but the businesses were shut down and roads were denied access to for
long periods of time. We were successful in getting an inspection team in the middle of
some interesting weather and Kroll has rejoined us as a certified lab open for business
again. I would like Pat Pizzo to make a couple of comments if she so chooses about
where the status of things are down there.
MS. PIZZO (Board member): First, I thank all of you for helping us get our certification
back as quickly as we did, the whole program made a concerted effort to help us get
certified and back into testing as quickly as possible. We are back and operational, the
city itself is going to be a long time in coming back as I am sure you all realize from
seeing the news. It has been an interesting experience and one that we hope not to have
to go through in another 40 or 50 years. It was a massive undertaking to go from a gutted
building to a certified lab in just three months, so it was an interesting experience and one
that I will long be retired before I do again. Thank you.
Agenda Item: HHS Update
DR. VOGL (DWP): We have a flier announcing an NLCP workshop to be presented this
summer. It been sent out to the laboratories in our program and other interested parties.
We want to make sure that the public is aware of it and are hoping that some of the
alternative specimen laboratory people would be interested in attending to get a better
understanding as to what is involved in the certification program which will eventually
apply to the other types of testing. I hope you can take this back with you, share it with
people that you think are interested in attending, and be sure to contact RTI, it is limited
to 25 attendees. As it states, if there is a lot of interest there might be an opportunity to
present the material more often or at least again in 2007, but we will see how that goes as
far as what the interest is.
The next item is our website. Our website is workplace.samhsa.gov and
we try to keep it updated, especially all the DTAB material, the transcripts, the agendas,
and the meeting schedule. The only information on the schedule besides the date is that
the meeting is in this building. You do need to keep view the Federal Register notice
when it comes out because that notice tells you when the open session is for the meeting.
We also attempt to contact all the people who attend the DTAB meetings on a regular
basis by email, usually three or four weeks before the meeting so they are aware when the
open session is and what some of the topics are, and can then contact our administrative
assistant as far as getting access into the building. It takes time to get people through
building security. It is important that we have a prepared list of people who want to
attend. It makes it a lot easier to get into the building.
The website is being migrated from one type of software package to
another. Half of it has been migrated while the other half has not. When you do go to
workplace.samhsa.gov site, it flips to dwp.samhsa.gov, but it is the same website and
eventually when everything is migrated then it will stay as workplace.samhsa.gov. If you
look at the link, you might think you are no longer on workplace.samhsa.gov, but you
are. It is taking quite a bit of time for the IT folks to migrate everything to the new
package they are using for the website.
On February 22nd we published a Federal Register notice regarding the
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Federal custody and control form. For those who use the form, the use of it expires on
July 31, 2006. We are in the process of getting OMB to approve a three year extension of
the use of that form for urine testing and this notice is part of the requirement on our part
to allow the public an opportunity to submit any comments on the form. We are not
changing the form. I have already received calls from a few people asking why we are
changing the form. We are not. If you read the notice, it is not changing the form, it is
strictly providing the burden hours that it takes to fill out the form and for a couple of
other items, like the lab application, and so there is a 60 day public comment period.
Once that ends, we will forward the entire package to OMB and hopefully they will clear
it in time for us to continue using the form after its current expiration date.
MR. STEPHENSON: I know that this is not part of the agenda, but I would like Ed
Jurith from ONDCP to make any comments.
MR. JURITH: Thank you, Bob. It is a pleasure to be here with you all this morning. As
you know, the issue of drug testing is important to the President’s National Drug Control
Strategy. Director Walters and the Administration have placed an emphasis on student
drug testing to give school district administrators around the country an additional tool to
help students avoid the lure of drugs. We have found looking at the research, looking at
the experience of many school districts around the country that schools that have
effective student drug testing programs in place give students an additional tool, an
additional reason to avoid the peer pressure and the other consequences that may lead
them to experiment with drug use. I think the support of the drug testing community in
general in terms of providing good technology, good lab certification, best practices, is a
help to the schools that choose to use this tool, not in a punitive sense, but really in an
identification and an intervention sense to help students avoid drug abuse.
Agenda Item: Nuclear Regulatory Commission Update
MR. MCCUNE (NRC): I would like to start off by reiterating a statement I have made a
number of times and, that is, the DTAB and the assistance role of SAMHSA for Federal
workplace drug testing programs is critical to just about every other government agency,
the NRC included. We have incorporated many of the current testing and processing
requirements from HHS into our current policy, 10 CFR Part 26, Fitness For Duty
Programs.
I would like to give you an update of where we are with the Part 26 since
the last DTAB meeting in December. The public comment period closed on Part 26, we
are currently still in the process of incorporating comments and deciding how to address
the concerns of the stakeholders that did comment. One of the chief areas that I think is
going to be the biggest challenge to us is what kind of drug and alcohol testing
requirements we have for our licensee plants during construction. Since the current Part
26 was developed in the 1994 timeframe really up until recently, about a year and a half
ago, the NRC had no plans to build new reactors and so licensees really were not
considering Fitness For Duty or any other policy that would impact that process. As you
are probably aware, through the President as well as the NRC we are onboard for an
expedited combined licensee process that really will have designs approved within the
next five years and new reactors being built. So the focus on all policy, not the least of
which is how you implement Fitness For Duty during construction, is really foremost in
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the industry’s mind, in the NRC as well.
We have determined without going into too much detail because our
decisions are yet made public that to have when the first bulldozer shows up at a green
field site a full up and running Part 26 program which is full access authorization and
Fitness For Duty testing and monitoring may not be feasible and so what we are trying to
do is work with the industry to develop kind of a middle ground for which we can ensure
that Fitness For Duty exists on construction sites for nuclear reactors but doesn’t present
an overly onerous regime for which licensees really cannot comply. I think it is safe to
say that we believe at the NRC that standard drug and alcohol testing programs that are
evident in the construction industry as a whole are really not appropriate because we are
not building office buildings, we are building nuclear reactors, and we want to make sure
that we use due diligence to ensure that design flaws or our adversaries do not have the
opportunity to build into nuclear reactor designs or construction things that should not be
there.
Within the next month and a half we will most likely have a public
meeting because the construction requirements for Fitness For Duty regarding Part 26
were not fully understood in the fall when the original rule went out for public comment.
We are likely going to have another public meeting so that we can roll out our new
concept for Fitness For Duty during construction. And that remains other then some
relatively minor aspects of the policy, the major sticky wicket if you will, but I will tell
you that it is our responsibility as it is really other government agencies to evaluate
current SAMHSA and HHS policy for incorporation into their programs and so we are
working very closely with SAMHSA and HHS, we are very interested in alternative
specimens, and somewhere down the line we will be doing a revision to Part 26 that will
implement alternative specimens and other cutting edge HHS policies as they are
applicable to the NRC.
Agenda Item: Department of Defense Update
COL SHIPPEE (DoD): I didn’t expect to be sitting at the front table here so I have
nothing prepared. But listening to Tim’s comments, as you know I’ve talked with
SAMHSA, DoD has looked at alternative specimens and saying it is not for us. As you
know, we have a big leg up on everybody else because we do observed urinalysis testing
so the impetus there for us to look at other methods has not been that important.
However, in the last year or so I have been coming under increasing pressure to get more
bang for our buck, there is no more money added to my budget, but I have to do more
like everybody else. I have looked at the military accession process, the entrance
stations, there are 65 stations around the country that bring new recruits into all the
services, and by our directive they have to do a urinalysis before they come into the
military. I have looked at that and asked myself why couldn’t we use saliva testing or
oral fluid, for example, because we do not litigate those and we have never had a
Congressional on a urinalysis drug testing in the MEPS situation. In that light, I turned to
the command that runs the MEPS, and offered this up. In looking at the literature, I
suggested that maybe what we ought to do is just run a pilot study and they agreed.
We have been at this for the last year and a half, looking at the Orasure
collection device, mainly because we have had a contract with them for reagents at the
Armed Force Institute of Pathology, that is the reason we went that way, and we are
going to look at, we are going to collect the oral fluid, along with urinalysis, we would
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not hold the applicant liable for the oral sample, it is just for the urinalysis, and run this
for probably about a year. We are set up to collect about 30,000 specimens.
It will be a nice study because I have tight control over both specimens. I
will be able to link the oral fluid with the urine very positively, and we will monitor as
we go along. As we get data, we will share that with SAMHSA.
MR. STEPHENSON: That is wonderful news. That’s the kind of contribution that
means a lot both now and will continue to contribute later on as we get into the systems
development.
Agenda Item: Department of Transportation Update
DR. VOGL: I contacted George Ellis (DOT) and he responded by email that he would
not be at the meeting. He did provide, in his email, a couple of items to present this
morning. He wanted to thank people for submitting comments to the DOT proposed
notice of rulemaking. As you are aware, they put out their notice soliciting public
comment to incorporate specimen validity testing into the DOT regulations. He goes on
to say that they received over 200 comments from actually 27 different commenters, so
obviously many people commented on more then one issue. He believes the comments,
wanted to say the comments were helpful, appreciated the public interest, and they are
presently working on organizing the comments and working on their development of the
final regulation, of course, as we know those things do take some time.
He wanted to mention that they are about to release another proposed
notice of rulemaking to allow marriage and family therapists, who are credentialed, to
become substance abuse professionals, better known as SAPs, into their program. He
expects this to come out in the next few days and again it would be for public comment.
I am sure they will receive responses on that request and then move forward with
eventually coming out with a final rule.
Those are the two items, that if he were here, he wanted to mention this
morning.
MR. STEPHENSON: At this time we are going to ask you all to take a deep breath and
get ready to be plunged into a lot of scientific data and graphs and images and the
purpose of these two presentations is very well focused, it is to take what it is we have
learned, what it is we still do not know and have to learn in the process of addressing
alternative specimen proficiency testing and controls development and designs. It is not
an issue of just showing problems or the current state, but to give us a benchmark from
which to develop an agenda to how to go forward. It is our goal and intention to take
action across a number of arenas and you can certainly participate in that process as we
go along.
Agenda Item: Pilot Performance Testing (PT) Program for Hair
Note: The PowerPoint slides for the following presentation are attached at the end
of the transcript.
DR. MITCHELL (RTI International): We will begin with the Hair Pilot PT Program that
we have been running and the most three recent cycles that we have had, that’s cycles 9,
5
10, and 11. Dr. Jeri Ropero-Miller is now the primary person in charge of the Hair
Testing PT Program. She has been with RTI for approximately a year, and this is the first
three cycles that she has designed and has carried out. We will look at the results, it is no
longer my bias as some people might think.
I regret that a lot of this is going to be very technical. We tried to provide
sufficient explanation and to look at things different ways to try to increase the
understanding of this by everyone, technical and non-technical.
Slide 1 – Title – NLCP Hair Pilot Performance Testing (PT) Program
Update Cycles 9 Thru 11
Slide 2 – Objectives
The objective of today’s presentation will be to review the design and
results of hair cycles 9 thru 11. As kind of an academic but yet informative process, we
are going to compare the results of these three cycles to the requirements of the proposed
Guidelines from April 2004. We have to remember that these are not the final criteria,
but they are what HHS published in April 2004, and also to disseminate future plans for
this program.
Slide 3 – Pilot Hair PT Program: Design of Cycles 9 Thru 11
Slide 4 – Pilot PT of Hair: Cycles 9 Thru 11
We will begin with the design of cycles 9 thru 11. In this cycle, we did
some things a little bit different, we are always working on the technology of producing
the samples themselves and in this one Jeri chose to do something that I did not attempt
and that was to put all the amphetamines into a single hair preparation. As you can see
that the first sample, or the prototype of the sample contained amphetamine,
methamphetamine, and the designer drugs MDA, MDMA, and MDEA. This is the first
time we did it and she was very successful in accomplishing the spiking the hair at the
levels that we desired.
The second type of sample that we produced was one that contained
cocaine, cocaethylene, which is a purported metabolite from people who take cocaine and
are also partaking of alcohol, and also another purported metabolite norcocaine. We did
not include in this sample benzoylecgonine or BE as you see in the third prototype
because one of the problems with cocaine that we found early on in urine is that it can
degrade or can be hydrolyzed to benzoylecgonine during extraction procedures. We
wanted to look at the ability of the laboratories to extract cocaine from the hair matrix
and were they or how good were their procedures such that they did not hydrolyze the
cocaine to BE.
The fourth type of sample would contain the opiates including 6-
acetylmorphine which is a purported metabolite of heroin, codeine, which we are all
familiar with, morphine, and oxycodone, and one of the reasons for oxycodone was to see
if this particular compound would interfere with either the determination of morphine,
codeine, or 6-acetylmorphine. The fifth sample was PCP, contains PCP, and the last of
course, our favorite from urine, the marijuana metabolite, 9 carboxy-THC.
Each of these samples were formulated at three concentrations, we had
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one in which the concentrations of analytes would be at 50 percent of the proposed
cutoff, that is, the proposed cutoff that was proposed in April 2004, at around the cutoff,
and at a concentration above the cutoff, somewhere around 200 percent of the cutoff.
Slide 5 – Pilot PT for Hair: Cycles 9 Thru 11
In these samples, they were not really formulated for initial testing, they
were more for confirmatory testing so we did not require or did not ask for initial testing
with immunoassay of these particular samples so the only results that we have will be
confirmatory results. In doing the confirmatory test we asked the laboratories not to
conduct their decontamination procedures that they use to try to remove analyte from the
surface of the hair, we had found in previous cycles that using these caused a great deal
of variation that we could not account for.
The shipment consisted of 19 spike samples as well as 2 user drug strands.
We had one that contained THCA and another one which contained some of the opiates.
We sent to the laboratories samples containing 50 milligrams of sample and the reason
for this is that even though the Guidelines call for the collection of 100 milligrams of hair
the laboratories would not be able to use that if we continue with the split sample criteria,
that is, there would be part of that sample that would be reserved for the individual or the
donor who was being tested, so 50 milligrams was what was the total amount that we sent
to the laboratories to conduct their testing.
We requested that the laboratories submit their results to us within 10 days
of receipt and they did a very good job this time of getting the results back to us.
Slide 6 – Pilot PT for Hair: Cycles 9 Thru 11
We shipped the samples in the timeframe from July through December of
2005. There were three shipments sent on alternate months. We had 9 participants and
we did not inform the laboratories of their performance until after cycle 11 had been
completed.
Slide 7 – Cycles 9 Thru 11 of Pilot Hair PT Program: Confirmation
Analysis
When a lab is to be certified or applies for certification, one of the things
that is important is that they meet certain criteria. I have laid out some of these criteria
just so we could look at them and look at the participants. The first one, by the way, we
just have the laboratories, we do not have their names, we just have a letter designation,
some of the laboratories were aware among themselves who participates but not everyone
is aware of everyone who is participating in this program and there is no requirement for
that.
We asked the laboratories to provide us some demographics of their
testing. The first one is how much sample do you need in order to conduct drug,
confirmatory testing for one drug. You can see that we had two laboratories that required
the entire sample amount to do confirmation for one drug class. That is excessive and
would probably not be acceptable in a certified program, it is just too much and it means
the laboratory couldn’t conduct initial testing to begin with and then if they had more
then one drug class they wouldn’t be able to conduct another confirmatory test.
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You can see that the others, and this is something that’s very nice, is that
the levels that are required have come down to somewhere between 10 and 20 milligrams
per test, which is getting in the range of acceptability. The thing that we start running
into is the sample decreases, there is also the problem of measuring that sample and
weighing it and 10 milligrams requires at least some specialized equipment like a five
place, at minimum of a five place balance and other things. That is all to be considered in
the certification process.
Second, is the sensitivity of the assays and the confirmatory tests that
they’re using. Are they capable of meeting the cutoff levels? In urine we require the
laboratories be able to confirm down to 40 percent of the published cutoff, that has not
been established yet in the hair, but I would expect that if a lab had a LOQ exactly at the
cutoff that that would not be acceptable. Those are some standards that are yet to be set,
but as you can see we had three laboratories that were unable to meet the cutoff level
with their confirmatory process.
We also had going to the next column current urine analytes, we thought it
wouldn’t be fair at this point in time to always just look at all analytes and not consider
the fact that the procedures, confirmatory procedures for certain analytes have been
worked out with urine and they’ve been extended into the hair and oral fluids, and so, and
they were the first ones that were worked on in the laboratories. We are looking at the
current urine analytes that will be analyzed in hair and you can see that most of the
laboratories were able to analyze for those even though their cutoffs might not meet the
LOQ requirements. We only had one lab and they could not confirm for the 9 carboxy-
THC.
Under the proposed analytes this deals mostly with cocaine which is not
currently tested for in urine, norcocaine and cocaethylene, as well as the designer
amphetamines, MDMA, MDEA, and MDA. You can see that some of the laboratories
are still in the process of developing their procedures for these particular analytes and
currently do not have them ready to be utilized in a testing program.
Slide 8 – Cycles 9 Thru 11 Highlights
In the past, our focus has been on the variation around a group mean and
that is looking pretty much at the accuracy of the program of the participants. We are
going to do something a little bit differently, we are going to look at the precision of the
individual laboratories today and so we’ll go through this, it is a new concept that we
have talked about ourselves and tried to come up with a way to explain this. As we go
through this, we’ll see if we can get this concept over because we are also going to look
at the same thing with oral fluids a little bit later. Also, we are going to look at the
performance of some selected participants and these are participants who had more then,
had analyzed these samples outside of the pilot PT program, and let me explain that
before we get into it, it is not necessarily an advantage for a laboratory because
laboratories that we use to give us some idea of our spiking process, whether it worked or
not, they’re given a lot of samples, some of which may end of being used in the program
and some which may not, so it is really not an advantage from that standpoint.
The reason we need to do this is that with hair there is no way to tell at this
point in time how much drug went into the hair when we spike it. In urine, we can put a
known amount, put a known amount into a volume and from that we can determine
concentration, but in hair that’s not possible at this point in time, we do not have the
8
technology. We depend upon laboratories to give us a ballpark figure as to where, how
much analyte we got into a particular hair preparation, and so some of the labs that we are
using that have more tests then were conducted inside the pilot PT program were asked to
do this, unknown to them they tested these samples prior to the PT program.
Slide 9 – Distribution of Within Laboratory %CVs for All Laboratories for
Amphetamines from Cycles 9 thru 11
First, we are looking at within laboratory percent CVs. The coefficient of
variation we use to look at the variance of values around a mean, for example, in this
particular part of the program the laboratories received the same sample three times, once
with each cycle. We took the three values, we determined a mean, and then we
determined the standard deviation. The coefficient of variation is merely an expression
of that standard deviation as a percent of the mean, and so it tells us well those values are
within plus or minus say 10 percent, or 20 percent of the mean, of the labs own values.
We are not looking at the lab, and so this ends up being kind of an indication of precision
that the laboratories were able to show during these tests.
In the column here, we have the five different amphetamines, we have
amphetamine, methamphetamine, MDA, MDMA, and MDEA. These are the five
analytes that we had in the hair. One thing that we can see here is that the variation for
individual samples varied. Now we are not showing whether there is no indication of
whether this particular sample was one at 50 percent of the cutoff or at the cutoff or 200
times the cutoff, it just says that that is a sample that was analyzed three times and the
variation in the analysis of that sample by that lab was looks like about plus or minus 90
percent of the mean of their three values, so that is a pretty high variation.
But the thing that I would like to point out is that down here we have a lot
of labs that are analyzing samples well within what we would consider acceptable
variation, somewhere around plus or minus 10 to 15 percent. And we have that on each
of the samples even though it somewhat decreases as we go across into the newer
analytes and that’s because probably we do have fewer determinations that have been
made.
One of the problems that we have always been worried about with the hair
since we do not know what’s in there, I mean exactly the amount, the question is are the
preparations so variable that laboratories will never be able to get precise results, that is,
consistent results from one test on one day to one test the next day or a month later, and it
looks like yes, we will be able to obtain with these preparations samples that will give us
the uniformity that we need in order to run this program.
Slide 10 – Accuracy and Precision
Maybe I should have started off with this slide, but I thought since we
have seen it, let’s talk about the difference between accuracy and precision. In the
previous slide we were looking at precision, in precision all that tells you is how are the
values grouped about a point. You can see here we have precision, but we also have very
low accuracy, if we had accuracy it would be like precision and accuracy would be
distributed around a known point or a point that we are trying to obtain. Accuracy on the
other point talks about how well do the values, the individual values when grouped
together predict the value that they are supposed to represent. Over here we have very
9
low accuracy because you can see if we tried to average these the middle would be
somewhere in there, so it is off of the center point.
These we have low precision, you can see we have scatter but they’re
scattered about the point that we desire in a pretty uniform way and therefore we have
accuracy but we have imprecision. When we look at the individual CVs within labs, we
are looking at either this point or this point, we can be looking at essentially what is the
precision of these labs.
Slide 11 – Precision versus Accuracy – Amphetamine
To go into this a little bit further we took some results from the
amphetamines and we determined the accuracy and precision using these CVs. This
represents the three values that were reported by a laboratory and we can see here that
this is within plus or minus, these values are within plus or minus 10 percent of the mean
of those values. However, by accuracy the mean differs from the mean of these values,
differ from the actual mean by 26 percent.
In going up, we see that with these three values we have a precision of 8
percent but the accuracy, how much they vary from the true value that we are looking for,
is 33, and again we have real precision, we are down to 4 percent, but the accuracy is off
at 41 percent. Now these values, this does not reflect a single laboratory, we picked
examples which were going to point out what we wanted to point out here this morning
as far as accuracy and precision, so do not try to infer any of these values to a specific
laboratory.
Slide 12 – Methamphetamine %CV Across Laboratories
We can look at the CVs for each of the samples for methamphetamine for
each of the laboratories and these are the within lab CVs again. One of the things that we
are looking for is what is the distribution of these samples within the CVs. One of the
kind of things that scientists think about is that the higher concentration within certain
limits then the better you’re able to determine that value, and so we are looking to see if
we have some type of bias within the system toward the higher levels, and the higher
levels is the green, and you see that we have green at high concentrations as well as, I
mean at CVs as well as the lower CVs. We can see the same thing with each of the
samples, at the samples at 50 percent of the cutoff you can see that we have labs which
are able determine them within 20 percent easily, we have others that are not. We do not
really a see an overall system bias due to the concentration, that is lower concentrations
are not as easy to determine as are higher concentrations, we do not see that in this
particular system.
Now for a point of reference, we have been talking about CVs and in hair
we are talking about CVs within laboratories, we want to try to show you what’s going
on in the urine labs to give you a point of reference and the urine of course is a mature
industry, we have been going since ’88 with this program and so the laboratories have
standardized their procedures pretty much, they’ve developed all the processes that are
needed.
Slide 13 – Distribution of Between Laboratory %CVs for All Urine
Laboratories from Occasion 77
10
Here we are not looking at within lab, we are looking between lab or
among lab CVs. And they can vary, if you have labs that are out, if you’re looking at the
population, you can see much greater variance in these and that’s one of the reasons we
are looking at the intra or the within lab CVs with hair today. With urine you can see that
the CVs of the samples, and we had five different samples for each analyte, this being
amphetamine, methamphetamine, THCA, BE, codeine, morphine, 6-acetylmorphine, and
PCP, and you can see that the CVs across the urine system are down around 10 to 15
percent overall, which is very good, and that’s where we’d like to see hair and oral fluid
as they mature.
Slide 14 – Between Laboratory Performance on Urine PT Sample 2009 for
Amphetamine
If we take the amphetamines and we look at the distribution of the 50 labs
and their values around the mean of this particular sample we’ll see that they all lie, well,
most of them lie within plus or minus 10 percent, and that’s what we’d like to see in hair
is that most of the values will lie within plus or minus 10 percent and certainly within
plus or minus 20 percent is the goal that we have.
DR. NIPPER (Board member): I just wanted to ask you about the X-axis on that chart,
that’s just the, from left to right that’s just the number of the laboratory that was doing the
testing? That’s not day to day or time or anything like it is usually on the laboratory
chart?
DR. MITCHELL: No, this is kind of a chart that we made up, what we did was we
plotted the values for the laboratories, we just numbered them one through 50 at random
and then put their values, plotted them on to this. This was just to illustrate the type of
distribution that we see in the PT program for the urine with amphetamine at this point in
time.
Slide 15 – Distribution of Within Laboratory %CVs for Cocaine and
Related Compounds from Cycles 9 Thru 11
Okay, I think we have talked enough about amphetamines, let’s look at
some of the other analytes within hair. You can see that this is dealing with cocaine and
related compounds, we have the cocaine, CE, BE, and norcocaine, and again we are
looking at the percent CV and each one of these representing three determinations on a
single sample over the three cycles by a single lab. And you can see again that we have a
number of laboratories that are able to obtain values that are down around the 10 to 15
percent. In norcocaine you see is actually pretty good, but we only have 9 determinations
so there is a limited number of labs that are doing this at this point in time. We do have
some acceptable precision with these particular samples.
Slide 16 – Distribution of Within Laboratory %CVs for All Laboratories
for Opioids from Cycles 9 thru 11
Looking at the opiates, again a similar situation as far as the distribution,
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we have some that are down below 20 percent but we also have variation that goes all the
way up to 60 percent, for in this case it is the codeine, and we are dealing with morphine
here and 6-acetylmorphine.
Slide 17 – Distribution of Within Laboratory %CVs for All Laboratories
for THCA and PCP from Cycles 9 thru 11
THC and PCP, THC as you realize is always in the urine over the years
has been shown to be very variable and difficult to spike into samples. I think part of
what we are seeing here is that, but also if you’ll remember the concentrations that we are
looking at in hair are, for the cutoff is 1 picogram/milligram which is, we are moving into
areas of trace analysis in essence and so we would expect higher variation if the
instrumentation is not capable of analyzing those samples. Also we are looking at other
variables such as weight and extraction efficiency from extraction distraction which
would affect these.
PCP is the old standby, but we do have considerable variation even with
the PCP.
Slide 18 – Comparison of THCA %CV Across Laboratories
Looking at the across lab CVs of the four different samples you can see
that we have considerable variation and we have some labs that were unable to do this.
Some labs were able to get down to the cutoff but couldn’t go any lower, also some labs
missed a 200 cutoff, 200 times the cutoff, so this would indicate that the procedures
really have matured for this particular analyte at the cutoffs that we are looking. We have
some labs that are able to go down to the 50 percent of the cutoff, which would be 0.05
picograms/milligram, and we have others that are not able to reach that.
The human hair, user hair here, is a fairly high concentration, it was up
between .8 and 1 picogram/milligram of hair.
Slide 19 – Performance with Amphetamine
Let’s look at, change the way we are thinking and let’s look at a couple of
things. Remember I said we were going to look at the performance of selected
laboratories, and these are laboratories that had more then three analysis of each sample.
We are looking at the, this blue is the mean of their determinations prior to the PT sample
being sent out. The mahogany color is the mean of the total, of all the laboratories over
the three cycles. And then the white is the, one of the laboratories, its mean and standard
deviation, and I didn’t point that out. This little extension on top of these bars is an
indication of the standard deviation for those particular, for their determinations. And of
course is the second lab.
As you can see that with this amphetamine we had fairly high standard
deviations overall, at the higher concentration, and it did not improve as we went down,
in fact one lab as we went down in concentration seemed to have some problems in
quantitating the sample and their variation was very high. The other lab on the other
hand had fairly tight down here standard deviations as we can see for amphetamines.
Now amphetamine I believe was about the best, the amphetamines are about the best that
we had overall.
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Slide 20 – Performance with Methamphetamine
Methamphetamine, now methamphetamine is one that when we started
this program many of the laboratories were analyzing for methamphetamine but not for
amphetamine. I think that’s reflected in that we see at the lower concentration fairly
good CVs on methamphetamine indicating that these laboratories overall, including the
group mean, have the capability of analyzing the methamphetamine at the concentrations
that we are expecting to utilize in the Hair PT Program.
Slide 21 – Performance with MDMA
MDMA, here we see some variability in the means of the laboratories, this
lab appeared to have a little bit of a high bias. We can see even though the standard
deviation for the determination by these two labs at the beginning was fairly tight. But
overall the standard deviation appeared to be fairly constant throughout the three
concentrations that we looked at with MDMA.
Slide 22 – Performance with MDA
MDA again, a similar situation in that we saw differences in the standard
deviations of the variability among the labs as well as their ability to quantitate this even
though they had been involved early on in a separate determination with a very tight CV
between these two labs.
Slide 23 – Performance with Cocaine
Cocaine, on the reference mean we did not have sufficient values to
determine a standard deviation so that is why this extension is missing off of here. But
we can see that the standard deviations, group standard deviations at the higher
concentration are higher, slightly higher then that of these two individuals, but overall
when we get down here the variations are very small. One of the things that we did see is
that there is very little conversion of the cocaine, there is some but very little conversion
of cocaine to BE.
Slide 24 – Performance with Benzoylecgonine
And for the samples that were BE only, did not have cocaine, we have no
contribution from hydrolysis of cocaine, we see that there is overall when we first
analyzed these samples we had a fairly high CV, or standard deviation, the group mean
was about the same, and the individual labs seemed to have that same type of problem.
And this was exhibited all the way through both concentrations.
Slide 25 – Performance with Cocaethylene
Cocaethylene, you can see at the higher concentrations we did pretty good,
but then we had down here, this is the type of variability that we’ll see, all at once we’ll
have outrageous values show up and I believe this was one laboratory if I remember
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correctly had, reported a value which was nonsense, it was so high that it was nonsense,
but yet it has to be included in the mean to demonstrate the type of variation that we can
see on samples in hair.
Slide 26 – Performance with Norcocaine
Norcocaine, we see the same thing here. On two samples we had
outrageous values, on another one we have a very tight CV and that’s pretty hard to
explain when we are looking at a PT program.
Slide 27 – Performance with Morphine
Morphine, we had high CVs in morphine. The question is is there
something happening to morphine in the hair. Overall, we had fairly high standard
deviations or variations for the morphine, whether it was in the initial testing or whether
it was during the PT program and so that is something that is going to take better
precision for us to be able to, across the system for us to be able to understand what’s
going on.
Slide 28 – Performance with 6-AM
6-acetylmorphine, there appeared to be some loss of material but if you
look at the group mean versus some labs but other labs it appeared to be on, so here we
get a mixed message from the analysis as being conducted as to what the true value of the
6-acetylmorphine is in a particular sample. We see that all the way across the three and
that yet has to be resolved.
Slide 29 – Performance with Codeine
Codeine, again we are seeing the typical variation in the group mean
meaning that we have individuals in the system which have an extremely high variability.
The two labs, their variability as a percent of their mean varies from sample to sample for
codeine as it does with other analytes.
Slide 30 – Performance with PCP
PCP, this is always, to urine has always been what people though it was a
gimme because it was fairly easy to extract from urine and was not hard to quantitate.
But with hair at least at the higher concentrations some labs appear to be having
problems, as you can see even the selected labs which provided some of the initial testing
have some issues associated with their values. Overall the PCP, especially at the lower
levels, appear to be fairly good at least for these two laboratories, so it is attainable.
Slide 31 – Performance with 9-Carboxy-THC
9-carboxy-THC, I have the three spiked samples here with the
concentrations down around the cutoff and lower, and you can see that the group mean
varied a great deal and I think that’s because of the methodologies that are being used in
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the laboratory, we haven’t, it is a challenge to get down to the 0.1 or lower concentration.
I think these variations that we see by these two labs are indicative of the type of
performance that we can expect and you can see here even with one of these laboratories
that gave us the initial value, which had a mean down here, their mean is high when we
look at their performance over three cycles.
With the user hair we see the same type of variation, we would expect
that. One of the problems that we have with user hair is the values that you can see in
user hair will be somewhat dependent upon the drug use patterns and since it is deposited
from the blood into the hair and so we would expect overall to see higher variability in
user hair then we would in spiked hair if we can get it in with spiked hair. So that’s why
we have been working primarily with spiking the hair to try to get uniform concentrations
across the hair. Again, with THCA, we are not only dealing with concentration
problems, we are dealing with THCA problems, that is the inherent instability of that
particular analyte.
Slide 32 – Performance with Opioids in User Hair
Performance of the opiates in the hair. You can see that with morphine we
had considerable variation, looking at it again, and this is the user hair, we had the
morphine and the 6-AM is much higher in this particular one but you see the variation is
still very great. Now there are a lot of user hairs we know from experience and talking
with lab, hair drug testing laboratories, is that in a person who is using frequently that
very, very high concentrations of these analytes are found especially 6-acetylmorphine.
However, we do know that in use by or recreational use of heroin, it may be chipping, I
guess it is commonly referred to as chipping, they may use one or two times in a weekend
and that’s it and so only you would have very spotty deposition into the hair and you
could end up with very low concentrations. And for the users we have never had a
problem, I mean the people who are addicted we have never had a problem, cocaine or
heroine in urine, we haven’t a problem detecting them but now with hair we do have
possibly the capability of looking at use over a longer period in people who have used
smaller amounts or infrequent use.
Slide 33 – Performance Testing and Certification of Hair Testing
Laboratories
That is the first part of looking at the actual data, let’s look at some
summaries. Before I do that I’d like to review the scoring guidelines for a laboratory that
is trying to become certified, and this is the initial hurdle that hair testing laboratories will
have to go over before they can become certified. Again, I am using those proposed
regulations from the April 2004 Guidelines.
Slide 34 – Section 9.6
Section 9.6 says what are the PT requirements for an applicant laboratory
to conduct hair testing? It starts off with an applicant laboratory that seeks certification
to conduct hair testing must satisfy the following criteria on three consecutive sets of PT
samples. One is have no false positives, now these really are essentially a direct
conversion or use of the current ones that are applicable to the urine drug testing
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laboratories. Second, one is correctly identify and confirm at least 90 percent of the total
drug challenges on the three sets of PT samples.
Slide 35 – Section 9.6 continued
Three, would be correctly determine the quantitative values for at least 80
percent of the total drug challenges, that means all challenges, all drugs, to be within plus
or minus 20 percent or plus or minus two standard deviations of the calculated reference
group mean. So of all the challenges that are given they have to identify and quantitate
them within 80 percent of the group mean.
Four, have no quantitative value on a drug concentration that differs by
more then 50 percent from the calculated reference mean.
Slide 36 – Section 9.6 continued
Five, for an individual drug, say for amphetamine, they must correctly
detect and quantify at least 50 percent of the total drug challenges. By correctly detect
and quantify, the quantify means within 20 percent of the mean.
Slide 37 – Laboratory Performance Compared
Okay reviewing all that, applying these standards to what we have seen in
cycles nine through 11. Okay, first, we had no false positives reported however
remember they were directed by drug class so they knew which drug class to test in the
sample and there was no initial testing which could have thrown a sample which
contained no drugs into a confirmatory batch. There was some restrictions on that but
those things will be looked at a later time.
Two, two labs correctly identified 90 percent of the analyte challenges
over three cycles. Now I thought that we ought to break that out a little bit and look at
the current urine analytes and see if there was any difference and we did. When we look
at only the urine analytes we found that 5 laboratories met this criteria, they were able to
identify 90 percent of these challenges. When we were looking at the new analytes, that
is cocaine, norcocaine, cocaethylene, MDMA, MDA and MDEA, two laboratories were
able to meet the criteria for these analytes. We will have some work to do within the
system at these other, with these other analytes.
Slide 38 – Laboratory Performance Compared (continued)
No laboratory quantitated 80 percent of all analyte challenges within 20
percent of the mean. All laboratories had one or more 50 percent quantitation errors.
And no laboratory quantitated 50 percent of all individual analytes within 20 percent of
the mean. We have some work to do and that’s what I am trying to point out to the
laboratories by this is that we have this hurdle, we have to determine how we are going to
get there.
Slide 39 – Pilot Hair PT Program
I think the first cycle that we sent out was in 2000, the purpose of the Pilot
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PT Program was to provide information on the state of the hair testing science, to help
guide the development and implementation with expanded mandatory guidelines. And
under that we had to develop appropriate PT materials for the certification program and
that was part of the purpose. It was also to provide the opportunity for interested labs to
develop accurate and precise test procedures before implementation of the expanded
guidelines. I think we are still working on this one.
Slide 40 – Variation in Hair Pilot PT Results
And the reason we are working on it, we are seeing large variation existing
among labs, and this is not within labs, among labs, and possible reasons are that the labs
are using a variety of methods for preparing the hair for analysis, we have labs using
powders, we have powdered hair, we have snippets, we have solubilization. We have to
come up with the process that is best and we are going to have to standardize that, the
process that’s best for removing, allows removal of the analyte from the hair matrix.
We also have varying methods for extraction of the drugs from solid hair
matrix. Some the extractions are just extractions of the whole hair itself, others are
extractions of a solubilized hair, and so the best method has to be recognized and
developed within the industry to provide, if we have any hopes of meeting the criteria
that were in the 2004 guidelines.
The next thing is that we still, we had labs who were conducting
confirmatory testing with a wide array of instruments and some of these do not have the
necessary sensitivity to meet the cutoff criteria and the 50 percent or 40 percent of the
cutoff criteria that will be in the guidelines, or I presume will be in the Guidelines.
Slide 41 – Variation in Hair Pilot PT Results (continued)
And we have large variations within labs and some of the reasons, and I
think one of the big ones right now since we are seeing precision is reference materials
are not commercially available and by this I mean reference materials that are at the
concentrations that we are looking at in hair. There are some SRMs available from NIST
but their concentration is very high compared to the cutoffs that we are looking for in this
hair program.
And not all labs have developed procedures that are accurate and precise,
we saw that we had precision in some labs but we didn’t have the accuracy. This could
be from sample measurement, the extraction procedures, variability there, and also of
course instrumentation always plays a part in this.
Slide 42 – Variation in Hair Pilot PT Results (continued)
Now the question we have is sample composition may account for some of
the variability but with the variability that we are seeing in the tested methodologies it is
going to be difficult in those particular instances to determine that. We do see and it is
very encouraging is that we do have labs that are able to provide results with CVs less
then ten percent, or around ten percent, and that indicates that maybe we do have some
consistency within these samples.
Working against that though with BE, benzoylecgonine, here we call it
BZE, sometimes we flip back and forth between BE and BZE in this program. This is
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benzoylecgonine and 9-carboxy-THC, they appear to change over time and so that is
something that I am not sure what we are going to be able to do on that but usually just as
with urine it is taken us since ’88 to work out a process that provides a stable PT sample
that we can, that has stability for long periods of time, I feel sure that we’ll be able to do
that with hair over time. These are challenges that we are going to have to meet in the PT
composition.
Slide 43 – Variation in Hair Pilot PT Results (continued)
And again the lab quality control procedures may largely account for
variability, we have the standards used to calibrate do not contain drug analytes at the
concentrations required for drug testing, we already talked about that, but these are the
standards that the laboratories are trying to use within their labs in the absence of
something that’s commercially available. And also the controls included in test batches
do not ensure accuracy and precision of the testing process, in other words we are seeing
variability within the controls that the laboratories are using.
Slide 44 – Road Map for Successful Implementation of Guidelines
What do we do? How are we going to go to the future if we are going to
implement these guidelines, or whatever the final guidelines are? We feel that part of the
problem may have been the way that we have been running the Pilot PT Program in that
we have three cycles in which the laboratories get no feedback, and so it is not until six
months later or four months later that they find out how well they performed and by then
they have probably changed controls, they probably changed their calibrators, it provides
a disconnect to the system. We feel that this, one of the things that we need to do is
increase the dialogue between the NLCP Pilot PT Program and the participant
laboratories to produce an exchange of ideas and solutions.
We plan to do this by having meetings or teleconferencing, webcast
meetings where we can have immediate feedback from the laboratories and feed
information directly to the laboratories about the most recent cycle. And review these
test results with the labs and encourage the group to work together as a group to develop
the solutions to the analytical problems.
The thing you have to realize is that urine started out with procedures that
had already gone through this process, through the military program. The military at the
time had been developing their analytical procedures since 1982 and they had standard
procedures by 1988, there were standard procedures almost in all the military labs even
though at that time it was the Army had their procedures, the Navy had theirs and the Air
Force had theirs, but still, they were standardized within. We do not have that pre-testing
or that pre-implementation process from a government agency and so it is going to be up
to the industry to get together and to work on their procedures and to improve the
message and come up with solutions to analytical problems.
Slide 45 – Road Map (continued)
We want to obtain a commitment from the labs to use these future PT
cycles as a resource to develop and improve their accuracy and precision. We also want
to use these cycles to resolve issues concerning sample stability and lab variation. And
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we are going to facilitate the development of appropriate calibrator and control materials
so that they will be available for the laboratories. And that commitment has been made
by the NLCP, HHS has given their approval for that facilitation.
MR. STEPHENSON: I told you this was going to be pretty intense and we are at a point
in time for a break. Let’s have a group process, think about how we want to do this, do
you want to hear the oral fluid presentation and see how much sticks from the process
that we framed for hair and apply it to oral fluids, do you have burning questions that you
just cannot wait to ask that you want to deal with hair first, either way we can
accommodate that, but let’s do it after the break.
MR. STEPHENSON: There is always a risk of reconvening a meeting when you’re
having such amazingly animated and interesting networking that’s going on as you stand
up and talk to each other, that’s also a part of the process going on even when you have a
break and I am glad you all were able to take advantage of it.
A couple of things I want to point out in the hair PT data analysis, there
are two things I want to advise or caution any of those who take one of these sets of
presentations handouts away from here. Do not try to correlate this to a specific lab, we
have been extremely devious and efficient in masking and randomizing the results, that’s
why in some areas you have alpha numerals for the alpha designators for the various labs,
and another set of data looking across labs or among labs we used numbers, and we
changed the relationship so you cannot go back and do A, B, C equals 1, 2, 3, it would
not work. And so with that caution it was not our intention to mask the ability of a lab to
understand their own values but we wanted to be careful not to do anything at this point
that would unintentionally destroy the credibility or efforts or intent or desire to work
together in the future.
What will happen in the future will be that we will work at getting the
information out quickly after each cycle, we will increase the number of individual
samples that are submitted, or the specimen types that are submitted to the labs, there will
be at least five tests within the cycle. We are going to look for consistency in analytic
ability within the individual lab and we are going to look at consistency of information
collected across the labs for a given specimen in a single cycle and working together as a
group we think that they’ll be some ways that we can do this. We also intend to approach
others in the Federal government who have responsibility for developing standards and
request that there is some work that’s done in that arena also.
There are several things that we are willing to put on the table and help
broker and help facilitate in a way, but it calls for the participation of the labs themselves
and a real commitment to doing the analyses consistently and doing as many of the target
analytes as possible to try to drive some improvement in this system or to learn where the
issues are to help us remove the variables that we can control as the program. That’s
what this is about, we have to get to a place that’s better then where we are, we think we
can, and it is going to be a joint process and we are willing to help make that happen.
Agenda Item: Pilot Performance Testing (PT) Program for Oral Fluid
Note: The PowerPoint slides for the following presentation are attached at the end
of the transcript.
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DR. MITCHELL: We completed the hair and then we cloned that as near as possible for
oral fluid so that some of the explanation that I’ve been through before I hope will not be
necessary, will not be as lengthy, and even though Bob gave me the same amount of time
it probably will not take the same amount of time to go through this because we are now
familiar with the formats that we have used.
Slide 1 – NLCP Oral Fluid Pilot Performance Testing (PT) Program
Update Cycles 4 Thru 6
The Oral Fluid PT Program has been run by Frank Esposito at RTI. He
has done a tremendous job running both the urine and the oral fluid, and in the future we
plan to spread out and Dr. Peter Stout will be running the oral fluid program in the future.
He will be able to give his full attention to it and I think that getting new ideas and new
approaches is going to help also in the oral fluid, just as it has in the hair over the past
year.
Slide 2 - Objectives
Again we are going to review the design and results of the Oral Fluid Pilot
PT Cycles 4 through 6. If you remember, we have gone through 4 through 6 before but
we are looking at them differently this time, we are not looking at the between lab or
among lab values, we are now looking at the precision that we see in the laboratories that
are doing oral fluid testing. We are also going to compare these test results to
requirements of the proposed guidelines of April 2004, and just as we did with hair we
are going to disseminate our future plans for this program.
Slide 3 – Pilot Oral Fluid PT Program: Design of Cycles 4 Thru 6
Slide 4 – Pilot PT of Oral Fluid: Cycle 4 Thru 6
Design of cycles 4 through 6. In this we had a series of samples, again we
are talking sample composition, amp and methamp, in these we were using human oral
fluid. We had the designer amphetamines together, we had cocaine and BE split for the
same reason that we had it in hair, we had 6-AM, codeine and morphine, all the opiates
together, we did not put oxycodone in this one. PCP and THC, now remember we looked
for THC, 9-carboxy-THC in hair and in urine but in oral fluid we’ll be looking for the
parent compound, tetrahydrocannabinol, as an indicator of marijuana use.
Each of the samples was formulated again at below the cutoff, the cutoff,
and 200 percent of the cutoff except for the THC, coke, and BE, which was at 300
percent of the cutoff.
Slide 5 – Pilot PT of Oral Fluid: Cycles 4 Thru 6
Again, we asked for confirmatory testing only. Each shipment consisted
of 21 spiked oral fluid samples and so the samples were sent each cycle to each of the
laboratories. We sent the challenge as 2 milliliters of oral fluid so we are only addressing
neat oral fluid at this point in time, none of the issues associated with collection devices
and things of that nature. We asked that the results be submitted by labs within 10
working days, unfortunately oral fluid was not quite as responsive as the hair was at that
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point in time, but I can look forward to better results on that in the future.
Slide 6 – Pilot PT of Oral Fluids: cycles 4 Thru 6
Now you see that these samples were back from 2003/2004 and it will
become apparent why I had to go back then in order to get these results as we go through
this particular one. We had three shipments that were sent during that period, we had 12
participant labs, and again as we did with the hair the results were provided to the
laboratories after we completed the third cycle which in this case was cycle 6.
Slide 7 – Cycles 4 Thru 6 of Pilot Oral Fluid PT Program: Confirmation
Analysis
Looking at the lab procedures and meeting the requirements to be a
certified laboratory we see that in the amount of specimen that’s required, usually it is
somewhere about 0.25 to 0.1 milliliters of oral fluid, and we see though that still we had
some laboratories which were requiring fairly large amounts, up to one milliliter in order
to be able to conduct confirmatory testing which is if you’ve ever tried to collect oral
fluid you’ll know that trying to collect 5 or 6 mLs of oral fluid would be a problem and
so I do not think that we would be able to utilize laboratories that had those high, where
the volume requirements were that high.
LOQ, everyone was meeting the LOQ requirements except for one lab
which did not have the sensitivity for the 6-AM. We had one lab that was not analyzing
for opiates from the current analytes that we are testing in urine. Of the new analytes you
can see that many of the laboratories did not have the procedures in place at the time of
these particular cycles.
Slide 8 – Cycles 4 Thru 6 Highlights
Again, this is the same, we are going to look at the quantitative variation,
the within lab variation, talk about accuracy and precision, and then look at the
performance of some selected participants. In this case, because of stability problems
with oral fluid we were making the oral fluid samples right before we sent them out for
the first cycle and did not have time to obtain reference values like we did with the hair.
But in oral fluid like urine you have a good idea of how much analytes you put into that
solution and so the concentrations we will talking about will be theoretical concentrations
which are going to show some things. And the selected labs again, we’ll show you an
example of one of the better labs on that particular sample and also one of the not so good
labs results.
Slide 9 – Distribution of Within Laboratory %CVs for All Laboratories for
Amphetamines from Cycles 4 thru 6
Okay, looking at within laboratory CVs for the amphetamines, three
cycles, and again we are dealing with the same analytes that we did with hair, we have
amphetamine, methamphetamine, MDA, and MDEA. And again we can see that
variability here in the oral fluid we have below 20 percent for amphetamine, we have
most of the analysis that were conducted which were 36 were at 20 percent or low. We
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can see the same thing for methamphetamine, most of them had a variable CV of 20
percent or low. MDA, we had many that were below 20 percent but we also had some
aberrant values reported by some of the laboratories.
Remember, these are the means of three separate determinations on a
single sample by laboratory. MDA, we have some that are down at 10 percent or less,
some within quite more, 20 percent or less, but we also have some values which are very
high and again these were the analytes that some of the laboratories had not developed
procedures for at, confirmatory procedures for at the time of these three cycles. And with
MDEA we do have some precision in here, some nice, but we are still, we are only
dealing with 9 determinations.
Slide 10 – Accuracy and Precision
Slide 11 – Comparison of Methamphetamine %CV Across Labs
I am not going to go through accuracy and precision again. Let us look at
comparisons of the three samples over all the participants, and again as Bob said, these
things have been pulled out of the hat and homogenized such that I cannot tell you which
lab is which. But we can see that we have within this population for methamphetamine
we have very good precision because all except for two aberrant values on a cutoff, that
is at 50 percent of the cutoff, are down below 20 percent. This looks very good for
precision for almost all of the laboratories.
Slide 12 – Distribution of Within Laboratory %CVs for All Laboratories
for Cocaine and Related Compounds from Cycles 4 thru 6
With cocaine we see a little bit of change, when we get to cocaine we find
that we do have laboratories that are below 20 percent but also we have variation here
and the exact cause of these, we cannot tell whether it is lab procedures or whether it is
something in the way they processed the sample and the same thing with BE. We have
not been able, we have not as yet teased out the information that we need. However, we
can see that we are able, on the same samples we are able to get a good precision among
the laboratories. Now we couldn’t, when we looked at these we could not, there was no
one sample that stood out as having a high variation.
Slide 13 – Distribution of Within Laboratory %CVs for All Laboratories
for Opioids from Cycles 4 thru 6
When we look at the opiates, the opiates as you will see presented some
problems, some challenges for the NLCP and we’ll talk about that but we have high
variation, you can see that this is not the same type of precision, number of labs that we
saw for the amphetamines. 6-AM you see we have very wide variation. But with
codeine we see some pretty good precision in many of the laboratories but still it goes up
to better then 30 percent in the precision.
Slide 14 – Distribution of Within Laboratory %CVs for All Laboratories
for PCP and THC from Cycles 4 thru 6
PCP and THC. This is PCP, you see most of the values are down here
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below 20 percent but we do have some aberrant values from laboratories. And THC is,
what’s going on here, we do not have any precision, so the question is what’s going on
here. We will look at this as we go through this presentation.
Slide 15 – THC %CV Across Labs
You can see that it doesn’t appear to be affecting one sample more then
others, they’re all having a problem, or the labs are having a problem with that laboratory
because we have very imprecise determinations being reported by the laboratories.
Slide 16 – Performance with Amphetamine
Now talking about with the selected labs first we have a theoretical mean,
which is the amount that was placed into the oral fluid, we have the value that the group
determined, and then we have the values of two of the laboratories, one having a very low
or very good precision as designated by the standard deviation here, and another one
which had a fairly high. But still relatively small for the population, not like some that
we have seen earlier. You can see that this pattern goes all the way across but this
laboratory, the bad laboratory, or not bad but the lab with the most variation is shown
here and you can see that there is a significant variation within that laboratory for
amphetamine itself.
Slide 17 – Performance with Methamphetamine
The same thing we see the precision, we have again the theoretical, the
group mean, looks like accuracy is pretty good overall, and we see that even with the
laboratory which had the higher variation their accuracy was pretty good. We see the
same thing except a little bit on the accuracy going out here, we see more variation on the
higher concentration, and that increases as we go up and we see the variation appears to
increase as we go up in concentration. Overall accuracy is pretty good when we look at
the mean, the group as a whole.
Slide 18 – Performance with MDMA
MDMA, very reminiscent at the lower concentrations of what we see with
the other amphetamines but as we go up we start seeing some aberrant values coming in
where the poorest performers, remember, this is a new assay, is fairly large compared to
what the mean of the values was, it would be at least, it looks almost like about twothirds
is the variation that they have.
Slide 19 – Performance with MDA
MDA, a very similar situation to what we see with the MDMA, we do
have variability within the group, do not know if this is real or what it may be due to the
variations but it would appear that the spiking, the amount that we are able to, we may be
losing some of MDMA, we do not know yet but hopefully we will be able to look at that
in the future because this value represents how much was put in, this is the group mean.
And the group means are very good with amphetamines but we do have an increased
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variability in some of the labs.
Slide 20 – Performance with MDEA
MDEA, this looks pretty good. The theoretical, the group mean, the best
performer, the poorest performer, not much difference at these lower concentrations. So
MDEA appeared fairly good performance, we did have some variation is still there
though with some of the laboratories.
Slide 21 – Performance with cocaine
Cocaine, in cocaine we can see that the means, the mean agrees well with
the theoretical in all three. Some labs have very small variability, others have larger
variability which is what we expected in this population, and so overall it is not too bad
but these laboratories that give this type may have problems in some of the PT samples.
Slide 22 – Performance with Benzoylecgonine
Benzoylecgonine, this kind of parallels what we see with the cocaine;
however, it appears that for some reason, and this may just be by numbers, mathematical,
that we ended up with the group mean being slightly less then what was spiked in to the
oral fluid. Again, we see the difference between the best performer and the not the best.
Their means are fairly close, but there is still a good bit of variability within the whole
population.
Slide 23 – Performance with Morphine
Morphine, we are seeing variability here, you can see that at this
concentration there is a decrease, it is even more pronounced as we go up in
concentration, so that would indicate that we are having a problem with stability of the
analyte, but also we are seeing large variation so the question is this due to variability in
the laboratories or is it due to the sample itself. We will try to answer that question as we
go on through here.
Slide 24 – Morphine Degradation During Cycles 4 Thru 6
And in answer to that looking at the same samples but looking at the
means over the three cycles and what we see is from theoretical over the three cycles we
see a decrease in concentration so this, a large part of this variability is due to instability
of morphine in human oral fluid, this is a sample problem, we cannot say that it is, we
cannot measure the problem with a laboratory, this is a sample.
Slide 25 – Performance with 6-AM
6-AM, as you can see when we look at theoretical and group mean there
does appear that there may be some decrease and we have high variability, we go to the
next slide, and here’s what we see is that we do have a decrease overall, it appears though
after that initial, after some type of initial decrease then the amount that we lose is not as
24
great so we do have some problem at least in, at least one of the cycles and that is the first
cycle we had some problems with stability of the 6-AM.
Slide 26 – 6-AM Degradation During Cycles 4 Thru 6
So that caused, that type of sample problem will increase the variability
that is observed from the values of the laboratories so 6-AM was not a good sample to
judge performance of the labs.
Slide 27 – Distribution of Within Laboratory %CV for All Laboratories
for Opioids from Cycles 8 and 9
Looking at the opioids, looking at morphine and codeine, looking at the
CVs of all the labs after we have hopefully solved the problem, this is in cycles 8 and 9,
these are later cycles, we went back and did some things to try to stabilize the morphine,
and you can see now we have a major number of the determinations which are down here
in the below the 20 percent and so that’s the type of performance we’d like to see. We
still, we do not know if this is due to sample or not with the 6-AM, that will, we will
continue to look at that and check that out over time on the stability of the 6-AM.
Slide 28 – Performance with Codeine
Codeine, we really didn’t see a significant decrease in the concentration
over time, as we can see here we are looking at the theoretical, the group mean, and the
best lab and the not best lab, and you can see that the group mean and the theoretical are
fairly close for the codeine. The standard deviation for the best of the performers is very
small and these are similar variations that we saw in other members of the participants.
Codeine seemed to be okay, it doesn’t seem to have the same problem with stability that
we have with codeine and 6-AM.
Slide 29 – Performance with PCP
PCP, I do not see a lot except that the variability, well, among the labs it
varies greatly, you can see that this lab is very tight and very close, this one is off by
maybe 30 to 40 percent with a large variation, that is the mean is, and the theoretical and
the mean tend to be fairly close, we may have had a small loss but you cannot really tell
whether that is driven by the variation of the laboratories and their accuracy. PCP is
usually thought to be a fairly easy analyte to work with, but we do some variability
among the labs.
Slide 30 – Performance with THC
THC, like I said, we had a problem with THC. RTI has been working
with THC for years and they find that the parent compound is even less stable then the 9-
carboxy, the metabolite, and so you have to do some things to stabilize it in solution. As
you can see in these, in neat oral fluid we had a great disparity between the concentration
that we put in and what was found by the laboratories. When you have that then you do
not know the rate at which it is degrading, whether all the samples are degrading at the
25
same rate and how they are handled in the lab, if they are unstable, they can increase the
instability for example. We sent these frozen to the laboratories, if they thawed them and
didn’t start testing immediately then you could expect more degradation in a lab then in a
lab that immediately started testing. We would expect the high variability that we saw.
Slide 31 – THC Degradation During Cycles 4 Thru 6
And just to point it out to you, looking at by mean, this is theoretical, this
is mean of the first cycle, second cycle, third cycle, you can see that there is a large loss
and then it slows down a little bit, but there is a loss of material over the three cycles as
was indicated by the previous slides.
Slide 32 – THC Performance from Cycle 7 in Artificial Oral Fluids
To try to solve this problem we went to an artificial oral fluid, there is a lot
of those in the literature and we came up with our own, I mean took one of those as a
basis and then modified it to stabilize the THC performance. We get very good
agreement between the theoretical and the group mean so it appears that we have solved
that issue of using artificial oral fluid. I am not sure that we will be able to use actual
human oral fluid in these particular samples for this reason, the inability to sterilize the
oral fluid to remove all the bacteria, and also the issues associated with the safe handling
of oral fluid. We are actually investigating and plan in the future to investigate the use of
artificial oral fluids containing the same components that you find in human oral fluid but
using this in this particular program.
Remember when we started, I said these 4, 5, and 6 cycles were from
2003, 2004, and 2005. As you can see we spent a large portion of our time trying to
solve issues that were identified in 3, 4, and 5 and that is, we are ready now to start back
with sending a full array of analytes to the laboratories, we concentrated on the opiates
and on the THC in 2005 and now we are ready to start looking again at all the analytes
now that it appears that we have solved the problems with analyte stability.
Slide 33 – Performance Testing and Certification of Oral Fluid Testing
Laboratories
We are going to go through the same analysis with the oral fluid results
and we will take some of these issues with the samples into consideration as we go
through this. Again, we are looking at the proposed guidelines as released for public
comment in the Federal Register, Volume 69, on April 2004.
Slide 34 – Section 9.6
Again, it reads the same, the oral fluid, except that, the actual standards
are the same, the only difference is it says oral fluid instead of hair. They have to meet
the criteria on three consecutive sets of PT samples, have no false positives, identify and
confirm 90 percent of the total drug challenges on three sets, over those three sets,
correctly determine the quantitative values of at least 80 percent of the total drug
challenges, that’s over the three sets, within plus or minus 20 percent, or two standard
deviations of the calculated reference group mean.
26
Slide 35 – Section 9.6 (continued)
Also have no quantitative values in which they have what we call a 50
percent error in the urine vernacular, in other words, did you quantitate a single sample
outside of 50 percent of what the group mean or reference mean is.
Slide 36 – Section 9.6 (continued)
The other one is for an individual drug, must correctly detect and quantify
at least 50 percent of the total drug challenges for that drug, and that means and for all of
them.
Slide 37 – Laboratory Performance Compared to Section 9.6
Again, no false positives, of course the same caveat, we directed the
confirmation, we did not do initial testing.
In spite of all the problems we did have one lab that identified 90 percent
of the analyte challenges over the three cycles. If we look at the urine analytes, we see
that 10 labs met this criteria and if we removed morphine and 6-AM which we had the
problems with in stability all 12 of the participants met the criteria. When we look at
cocaine, the new analytes, cocaine, MDMA, MDA, MDEA, and THC, one lab met the
criteria and if we removed the THC, two labs would have met the criteria. This reflects
that we will have some development to do on these particular analytes in the analysis at
that point in time.
Slide 38 – Laboratory Performance Compared to Section 9.6 (continued)
One laboratory quantitated 80 percent of all the analyte challenge within
20 percent of the group mean. If we remove morphine, 6-AM and THC we had two labs.
Now what does that tell you? That tells you that we still have some issues if only two out
of that 12 were able to meet it.
For the urine analytes we can see that 7 labs met this criteria, if we remove
the morphine and 6-AM results 10 labs met the criteria. For cocaine, for the other
analytes, one lab met the criteria without any correction because of analyte stability, if we
remove the THC, 2 labs met the criteria. Again it appears that most of our issues are
dealing with the new generation of analytes.
And I do want to, as a reference, many of these same analytes, especially
MDMA, MDEA, MDA, are going to be required in urine and I am not sure our urine labs
have all their procedures developed yet. We have not put them under the spotlight and
that will probably start sometime in the not too distant future and I will be up here talking
about them and where they are progressing. I just wanted to put it in the proper
perspective at this point in time with all of the matrices that we are working with.
Slide 39 – Laboratory Performance Compared to Section 9.6 (continued)
We had 2 labs that had no quantitation errors greater than or equal to 50
percent of the group mean. For the urine analytes, we have 5 laboratories and if we took
27
out the morphine and 6-AM, we would have had 8 laboratories. For the new analytes,
new generation, we had 3 laboratories that met this criterion and without THC we had 5
labs that also met the criteria for those analytes. It looks like in the oral fluids we are
making some progress towards the new analytes.
Slide 40 - Laboratory Performance Compared to Section 9.6 (continued)
No lab quantitated 50 percent of all individual analyte challenges within
20 percent of the mean. Urine analytes, 2 labs met this criterion, without morphine and
6-AM, 9 labs would have met this criterion. And one laboratory met this criterion with
all of the analytes and without THC we had 3 labs that met that criterion.
Slide 41 – Pilot Oral Fluid PT Program
The purpose, we have already gone through this, was to provide
information so that this program could be developed for the Federal government, the use
of this analyte, and so that the expanded Guidelines could be developed as well as PT
materials to support that. Ss you can see, we have had quite a few labs that have taken
the opportunity to work in the PT program and develop procedures for the analytes that
will be included in the new guidelines.
Slide 42 – Variation in Oral Fluid Pilot PT Results
There are some issues, we have some excessive variation among the labs
and again, probably the wide array of instruments, not having necessarily sensitivity,
appears to be an issue in some places. Another issue that we found was relating the
information, doing the math and relating the confirmatory results to the neat oral fluid
and there is some reasons for that because of the way they are operating now and what
we are asking them, the way we are asking them to do things, so there is some reasons for
that, that may produce some of the variation, may even account for some of the very high
values that we have that did not make sense.
Slide 43 - Variation in Oral Fluid Pilot PT Results (continued)
Also failure to use standards from sources outside the laboratory, this is
something that is extremely critical to the urine drug testing is having standards from an
external source so that you can determine if you are making the standards within your
laboratory you know if you are having a problem with what you have made or if you
purchase all, some of the labs even purchase all their standards and controls from a
commercial source. I am not sure that this is available or being used at this point in time
in the oral fluid, well, uniformly throughout the oral fluid industry. And of course the
instability of the morphine, 6-AM and THC, we cannot forget that that is part of the
excessive variation and it is some of it that we observed.
Slide 44 - Variation in Oral Fluid Pilot PT Results (continued)
Within labs, instability was definitely a problem, the reference materials
that are not always available commercially may be a problem with the oral fluids. The
28
laboratories need to work on their accuracy and precision in the sample measurement.
Oral fluids, because they are kind of viscous, can be an issue, and also use the best
extraction procedures and the best instrumentation procedures, make sure they have the
required sensitivity and repeatability.
I guess I am beating a horse, but I have to since it is my responsibility,
stability of the analytes, we definitely had problems but it appears that we have solved
those problems in the PT cycles that we conducted in 2005.
Slide 45 - Variation in Oral Fluid Pilot PT Results (continued)
I have already talked about this, lab quality control procedures may
account for some of the variability in some labs, and using standards and controls from an
external source.
Slide 46 – Road Map for Successful Implementation of Guidelines
Just as we have proposed for hair, we want to do the same thing, we want
to increase the dialogue between the NLCP and the laboratories that are participating.
We are going to do this through the same mechanisms that we proposed for the hair, we
are going to hold meetings as webcast meetings, thank goodness for the web, it makes it
very easy now to have participation from multiple participants from multiple locations, so
we are going to make use of those resources in this program. We are going to review the
results of the test that they have conducted and go over those with the laboratories and
encourage them to, just as we are with the hair encourage them to improve their methods
and come up with solutions to problems, especially analytical problems.
Slide 47 – Road Map (continued)
We want to obtain the commitment from the participants to use these PTs
to prepare themselves for certification whenever the guidelines will permit that. To use
these cycles that we will be sending out to resolve issues of sample and lab variation as
well as start looking at the immunoassays, remember it has been a long time since we
have looked at the performance of immunoassays in the system and that is coming up in
the near future. We have not surveyed the industry at this point in time as far as the
availability of the standards and controls like we have in the urine drug testing system,
but we are going to look at facilitating the development of those materials for the use in
the oral fluid at the levels that we need them to be to support this program.
MR. STEPHENSON: Thanks, John and the RTI team, you all did a great job of going
through the process and assembling this and we really beat them up pretty significantly
over the last week trying to get some internal consistency and be very clear of what was
being said. At the risk of now muddying some of the clear understanding, the very last
slide that we had put up on the oral fluid and pretty much this reflects the same thing with
hair, that we want a commitment from the labs that are participating in these PT programs
and the industries to use the materials and resources that we are committing to help drive
the industry and the performance of individual labs to a level that they will be able to
successfully apply for and become certified to perform testing using that specimen.
This is not a program that is designed nor can we tolerate the use of our
29
PT specimens and materials simply for fun and games, these are very expensive to
develop, they come at a cost that is distributed to the taxpayer funds, they are not
reimbursed by the individual contributions from the labs because there are no applicant
labs at this time and we have great variability that’s occurring amongst the participants so
far. We ask the labs and the industry itself to look in your own hearts, look in your own
pocketbooks, look at your own commitment, are you really interested in getting into this
and if so join in the process individually and collectively to work with us and with each
other to develop the standards across the industry such that they will generate good
performance over time. There are a lot of us that are invested in this process to make it
work and we are willing to commit the resources that are necessary to do that but we
have to engage everybody equally in this process over the reasonably short future in order
to get us to a point where we are able to do more then what we are able to do right now.
Accept that for what it is, we have to demonstrate that we can do some
things, I am not asking for a pint of blood from anybody, I am not asking for any kind of
commitment other then maybe they’ll be some agreement that we’ll put together, that will
come out, restate this, it is not a contract but it will be an understanding between the
participants in the laboratory environments and the program. Then participate in the
meetings and share the information, share the data and share your own insights because it
is collectively we have to perform better. What we will give back is more timely updates,
changes in the challenges to meet the needs as we evolve them, as soon as we get
clearance for final parameters of the mandatory guidelines in these specimens we’ll refine
and redefine the standards as they’re necessary, make sure that they get out in a timely
manner, and begin to do that level of work until we are able to demonstrate proficiency
across the group.
Is that acceptable to the board as a challenge? Because you have to be our
partners in this part of the process and with what we are talking about with oral fluid I
think this is something that if it can help you as a benchmark, as a beginning point, and
then sharing back information over time this will greatly help do this systems
improvement for both sets of parties.
COL SHIPPEE: Are you using a racemic mixture in your amphetamines?
DR. MITCHELL: No, it is all D isomer.
COL SHIPPEE: It is all D. The second question is when do you expect or how do you
expect to bring in the decontamination process in the hair as a variable in the labs?
DR. MITCHELL: I do not think we truly understand all of the decontamination and its
impact, and at this point in time I cannot address that.
MR. STEPHENSON: I think one of the things that we’ll do is we’ll have that as one the
elements we’ll engage the industry on and the labs that are participating because it is
clear that you might get one or two labs that can perform to a level of satisfaction but you
cannot drive a cost effective or an efficient system with just one resource out there, just to
participation in the certification if distributed amongst the participants, was that the cost
for an individual applicant lab could be horrendously high and by definition that’s the
way our cost sharing has been developed over time. We are absorbing all of these costs
now, but at a performance level later on for application and for maintenance and for PTs
30
they will be distributive costs. It serves everybody to have a larger group of participants
and we think there will be, but as an objective outsider, maybe you want to participate in
some of those discussions too even though you do not have, you know, well, as long as
you bring your body armor it will be all right.
DR. COLLINS: This is with regards to the hair, I wondered how close was your
reference lab mean to what your targeted concentration was? Was there reasonable
agreement or not?
DR. MITCHELL: If I understand your question you’re saying how close was the mean
to the theoretical, or what we considered theoretical?
DR. COLLINS: Right, with your reference labs.
DR. MITCHELL: Most of them were within 20 percent, this process that we have we
have been working on for years and Jeri has refined it beyond what we had done
previously and she’s getting most of the concentrations within about, within 20 percent of
what she would predict them to be, and again, it is not really a theoretical, it is a guess
based upon experience and based upon the performance of hair and it is uptake. After
you characterize a hair you can predict within a 20 percent or so what, and under
conditions, set conditions, what concentration you will find.
MR. STEPHENSON: We have answered all your questions but it is a little bit mind
numbing as the process, the amount of information and the process that its been presented
tends to overwhelm you just a little bit. As you go away from this presentation and if
there are some questions that you have, think about them, and then we can readdress
them either this afternoon or tomorrow morning as follow-up in the next part of our
meeting.
I think we have pretty well clarified everything that we had to present for
this part of the session. I am very pleased with what they were able to do. We will have
an opportunity after we break here for a little bit of that stand-up internal networking
before we reconvene in closed session. There will be an opportunity for having some
dialogue yet amongst interested parties, not necessarily sure about the amount and detail
of feedback we can provide at this time, but at least it will be an opportunity to have
some dialogue.
At this time, we have two individuals who indicated they would like to
make a public comment. About 10 minutes apiece. Again, this is an opportunity to make
comments, there will not be a response and we will not engage in a dialogue on the
issues. You are welcome to make the comments and they will become a part of our
transcript.
Agenda Item: Public Comments
DR. SOIFER: I am Professor Steven Soifer from the University of Maryland, Baltimore,
and also the staff director of the International Paruresis Association. Thank you for the
time to present to the committee.
On April 13, 2004, SAMHSA published a notice in the Federal Register
for revisions to the Mandatory Guidelines for Federal Workplace Drug Testing Programs,
31
69 FR 19673, FR Doc#04-7984. Public comments were submitted, or were to be
submitted by July 12, 2004. There were 285 public comments submitted, the members of
our organization, the International Paruresis Association, submitted roughly one-third of
them.
Both in those comments and at these hearings you have heard members of
our 1,000 person strong organization explain why accommodations must be made for
people suffering from paruresis, or shy bladder syndrome.
Today, I am here to say that it is simply unconscionable that the new
Federal regulations have yet to come out, almost two years after they were first
promulgated. What could possibly be the reason for such a long delay? Thank God we
are not dealing with a Federal emergency like Hurricane Katrina.
Because of the length of the delay, members of the IPA have had to enlist
U.S. Senators and Representatives in their home states to look into why there has been
such procrastination in releasing these regulations. Moreover, we are particularly asking
our Senators on the Health, Education, Labor and Pensions Committee, HELP, and
Representatives on the House Energy and Commerce Committee, which oversee
SAMHSA, to find out why there is a problem.
Hopefully, when we return here in three months the newly proposed rules
will be out and this will no longer be a problem. All we need are more Congressional
hearings on why our government isn’t working efficiently these days.
Thank you.
MR. STEPHENSON: Thank you for your comment.
MR. SPEIDEL: My name is Paul Speidel. I work at Psychemedics Corporation. I just
had a question, but you addressed it essentially which was the status of the proposed
guidelines. The comment that I did have though is if there is any guidance that you might
be able to provide, either in these meetings or some other way where we could find out
where the guidelines are, in other words not just the status but where they actually might
be in the process, perhaps maybe these meetings are the best way.
MR. STEPHENSON: This is always one of the more delicate things about government
and process of review and timing and again for both commenters, a generic response that
there are multiple levels of review that a document and a process like this go through.
The first groups are internal construct validity and scientific accuracy within the
Department, those have been done and completed. The legal reviews that are done for
consistency with government regulations from process are undertaken by attorneys and
those have been done. The third level of process is external to the department in looking
at the larger role of government and process across multiple government agencies with
multiple needs and agendas that have to be satisfied in aggregate over time and to make
sure that all thoughts have been considered and so that process has been undertaken and
inputs collected although we haven’t seen them yet.
There has not been a time to my best recollection where it has taken us
more then about a week to address issues that have come back through edits and
comments. The point is that they are not being held at our level and they are not being
held internally. The concerns that always come up and that always throw a monkey
wrench into the precision of a stopwatch is what happens if someone presents something
new that you haven’t thought of that is scientifically valid and it is challenging to the
32
point that you do not have answer for it, and that’s always the risk. To this point that has
not happened, we have been able to accommodate to the public comment process and
through the reviews the ability to address those kinds of variables to the point that there is
satisfaction, one, that we have been responsive to the public comments and second, that
we have been responsive to the science and the precision that we need to address in
developing these.
But these are a big deal and when you look at them over time getting them
right is going to be an important benchmark starting point. We have learned in earlier
iterations of mandatory guidelines for urine that often an industry or those who produce
materials, assays, instrumentation, for testing that’s performed in this arena will not take
action until there is a final published guideline, until there is an actual define aiming point
that the government has committed to and an implementation date that establishes a
window of opportunity. What will happen is that you can see some of the things that will
start to evolve under their own impetus once there is published guidelines. There is
nothing that we want more then to get the guidelines out the door with an implementation
timeline and an opportunity to begin to work on refining and defining those remaining
variables that we need to fix and to get the system up and running.
I cannot say any more because I do not know any more, but I have shared
with you very openly and honestly the philosophy that’s there, it is not derogatory or
condemning of any party in the process, but this is a huge issue that cuts across this
whole society, and quite honestly there is nobody else on this planet who is doing this
kind of work at this level compared to what we are. We are gathering interest from other
parts of the globe and the issues that we are addressing will be informative to them and
the things that others are doing across the other parts of this planet will certainly continue
to help influence the things that we develop too.
That is the end of the public comment process.
The open session was adjourned.


Hair testing is the most accurate and effective method of finding users of drug abuse.

Using a small sample of hair cut from the scalp, hair analysis evaluates the number of drug metabolites embedded inside the hair shaft.

When compared to more traditional forms of testing (i.e, urine testing), hair samples can detect a longer period of drug use. With urine, most drugs are undetectable if urinalysis is carried out more than 2-3 days after use, with the exception of cannabis, which may be detected for slightly longer periods of time.


After the 2-3 day period, a urine donor will test negative and slip through the urine screening process. With hair samples, the only time limitation for detecting drug usage is imposed by the length of the donor's hair. Every half inch of head hair in length provides a 30-day history of drug use.

The standard for the industry is to test 1.5 inches, which provides a 90-day history of the donor's drug use.

If no head hair is available, body hair can be used. This provides longer window of detection of approximately 365 days.

Bleaches, shampoos and external contaminants (i.e. cannabis smoke) have no known impact on the results.

Trimega Laboratories partner with a national nursing service who are trained to collect hair samples from your clients.

More about Hair Drug Testing

Hair Testing FAQ


1. What is Hair Drug Testing?
Since hair growth is fed by the bloodstream, the ingestion of drugs of abuse is revealed by analyzing a small sample of hair. Our testing method measures the drug molecules embedded inside the hairshaft, eliminating external contamination as a source of a positive test result. Hair testing results cannot be altered with shampoos or other external chemicals.


2. What drugs are included in a standard Hair Drug Test?
Cocaine, marijuana, opiates (Codeine, Morphine & 6-monoacteyl morphine), methamphetamine, (Meth/amphetamine & Ecstasy), and phencyclidine (PCP). These five drug classes are mandated for testing by the Federal Government.


3. What time period does a standard test cover?
A standard test covers a period of approximately 90 days. The hair sample is cut as close to the scalp as possible and the most recent 1.5 inches are tested.


4. Does hair color affect results?
Hair color is determined by the amount of melanin in the hair. It has been shown experimentally, through actual hair samples, as well as determined in court that hair color has NO basis in fact.

5. How fast does head hair grow?
Studies indicate that head hair grows on the average approximately 1.3 cm (or 1/2 inch) per month. This growth rate varies slightly (estimated at ± .2 cm per month),
consequently there is some (± 1 week) time variation possible.


6. How much hair is needed?
A standard test with GC/MS confirmation requires 60+ milligrams
of hair or approximately 90 to 120 strands. The thickness of different types of head hair (thick coarse vs. thinning fine) is the reason for this variation.


7. How does Hair Testing compare to urinalysis?
The primary differences are
1) wider window of detection
2) inability to tamper with the test

Cocaine, methamphetamine, opiates and PCP are rapidly excreted and usually undetectable in urine 72 hours after use. The detection period for hair is limited only by the length of the hair sample and is approximately 90 days for a standard test.

At this time there are no known adulterants for hair tests. Since hair tests analyze the drugs inside the hairshaft, external contaminants/chemicals have no effect.

Additional advantages include non-intrusive collection procedures, virtual
elimination of test evasion.

The combination of an increased window of detection and resistance to evasion makes Hair Testing far more effective than urinalysis in correctly identifying drug users.


8. How soon after use can a drug be detected in hair?
It takes approximately 4-5 days from the time of drug use for the affected hair to grow above the scalp. Body hair growth rates are generally slower and cannot be utilized to determine a timeframe of drug use.


9. What is the shortest time period that can be evaluated?
The minimum time period is approximately two weeks (1/4 inch). Body hair can be used if head hair is too short for a test. If body hair is used the timeframe represented by the test is approximately one year, due to the different growth pattern in hair below the neck.


10. Can tests be run on people with little or no hair?
Hair can be collected from several head locations and combined to obtain the required amount of hair. In addition, body hair may be used as a substitute to head hair. In the rare case where no hair is collectable, complete urine/adulteration testing may be utilized.


11. Does body hair give the same type of results as head hair?
Yes, body hair can be used to test for the five standard drug classes, though body hair growth patterns are different than head hair. Most body hair is replaced within approximately one year. This means a test done with body hair will be reported as drug usage during approximately a one year timeframe.


12. Can hair collected from a brush be used?
Yes, but the test will be reported as having an "anonymous" donor. We cannot attribute the sample to any specific person and we cannot determine the timeframe of the test, so the test result is not legally defensible. The test will only report that the sample submitted had the reported drug metabolite components.


13. How does Omega Laboratories establish its cut-off levels?
Omega follows the cut-off levels generally accepted industry-wide. These levels are based in part by minimum detection levels for GC/MS confirmation.


14. Does Omega Laboratories perform Gas Chromatography Mass Spectrometry (GC/MS) confirmation of all positive hair results?
Omega provides confirmation utilizing GC/MS for all specimens that screen positive (opiates, PCP, methamphetamine, cocaine and marijuana).


15. Can hair be affected by cross-reacting substances such as over-the-counter medications?
Enzyme-immunoassay antibodies (EIA), similar to those used to test urine, are used for the initial screening test for drugs of abuse in hair; therefore the potential for substances such as over-the-counter medications to cause a false positive screening result does exist. To eliminate the possibility of reporting a false-positive due to cross-reactivity, Omega confirms all positive results by GC/MS for methamphetamine, opiates, PCP,cocaine and marijuana.


16. How effective is Hair Testing in detecting drug users?
In side-by-side comparison studies with urinalysis, hair drug testing has uncovered significantly more drug use. In two independent studies hair drug testing uncovered 4 to 8 times as many drug users as urinalysis.


17. Does external exposure to certain drugs, like marijuana or crack smoke, affect the Hair Test results?
To rule out the possibility of external contamination, Omega testing (where appropriate) looks for both parent & metabolite (bi-product) of drug usage. For marijuana analyses, Omega detects only the metabolite (THC-COOH) . This metabolite is only produced by the body and cannot be an environmental contaminant.


18. Is Omega Laboratories' internal chain-of-custody comparable
to a urinalysis laboratory test procedure?

Omega's internal chain-of-custody is modeled after Federal guidelines (SAMHSA) as well as other accredited agencies (CAP).


19. How long are test reports kept on file?
Test reports are retained for a period of two years or as mandated by law.


20. What is done with the excess hair that is not tested?
The hair not used from the time period being tested (i.e. three months equals 3.9 cm) is stored in the chain-of-custody sample acquisition pouch. Hair is stored for a two year period.


21. What experience does Omega Laboratories have in providing
Expert Witness Testimony?

Omega Laboratories' forensic experts have qualified as expert witnesses in Ohio, New York, California, Texas, Nevada, Oklahoma, Alabama and Arizona in over 250 civil, criminal, and Superior Court trials.


22. What other drugs are available to be tested in hair analysis?
Currently, nicotine, methadone, simple benzodiazepines, tricyclic antidepressants assays and mescaline have been detected in hair. However, many details such as cutoff levels and dose response relationships have not yet been established for these compounds. Currently these assays are in the Research and Development process.

For more information please visit Omega Labs

TOXICOLOGY SERVICES

American Toxicology Inc. (ATI), is the ONLY laboratory in Nevada exclusively dedicated to drug testing. ATI, established in 1982, is the largest privately owned drug testing laboratory in Nevada, offering court-approved drug testing through competent screening and confirmatory tecchnology. ATI, does 100% of its analysis locally thereby reducing the possibility of loss, delay or misappropriation of specimens.

Our Services

Pre-Employment Screening
Post Accident Testing (24/7)
Probable Cause Testing (24/7)
Random Testing
Out-Patient Testing
24 hour turn around on negative samples
Complete confidentiality (only authorized people receive results)
On-site Drug Collections
Drug Testing Only - Clients wait time for collections is minimal
Medical Review
DATIA Certified
DOT

ATI offers affordable drug testing programs with the fastest turnaround times in the industry. ATI also offers expert witnesses in all aspects of drug testing and in the interpretation of drug test results. ATI provides, free of charge, additional analysis and testing interpretation of any client results found to be in question or in need of future inquiry.


ATI Hair Drug Testing History

My purpose for writing this article is to lay a foundation for American Toxicology’s hair testing and to assist those who are contemplating using hair testing for their workplace drug testing. Questions often arise about how accurate hair testing is, how save it is and how easy is it to administer. I hope to satisfactorily answer those questions.

In 1989, I believed in the school of thought that hair testing was too problematic to be used for drug testing in any arena. I had no personal experience to support my views. It was all based upon things I read. There were only a few scientists supporting hair testing at that time. I was approached by a District Court Judge who wanted to investigate the possibility of using hair testing in child custody cases. I was performing urine testing at the time for this judge, as well as for other judges, and he said the interest was not just his own.

So I began researching hair testing in my own laboratory, but with a bias against it. I had been an expert witness for the courts since 1972. I had been used extensively by the District Attorney’s office and had built up a reputation for being a reliable witness in forensic drug testing in thousands of cases by that time. Hair testing would have to prove impeccable before I would ever testify to any result coming from it. At the time, I did not believe this would happen.

As I began the research, I became intrigued right away. It gave me enough interest to continue on, spending hundreds of hours at a time. I knew in order to use the test in District Court, a positive result had to be true indication that someone had, without doubt, used drugs. The test had to know the difference between outside contamination and personal use. This was especially critical when one spouse used drugs and the other did not. Also, because in child custody cases one spouse generally knows what the other is doing, the test had to show true negative results. False negatives would cause as many problems as false positives. So the research proceeded with this in mind.

After about 18 months of research, I had changed my mind about hair testing. It was showing to be a true and accurate test. My main source of hair samples to conduct the research came from known users in Parole and Probation or Methadone Clinics. I was performing urine drug testing for these organizations at the time. However, in my research, I discovered that marijuana use was not testing accurately. But the other drugs, or “hard drugs”, were testing very well. Finally, I was ready to use the hair test I developed in actual cases. I was personally convicted of its accuracy for the hard drugs. But I knew it still needed to be tested in court. Now, it is important at this point for the reader to understand that there is not just one way to perform hair testing.

The method I developed is not the same as the methods used by other hair testing laboratories. Most publications about hair testing involve methods used for small number of samples. I developed a method that could handle a large number of samples rapidly. At the same time, the results had to accurately depict the true drug user. This required special procedures that remain, to this day, unique to ATI’s hair testing. At this time there was only one other laboratory in the country that performed hair testing in mass volume. They had since patented their procedures. I made certain that the method I developed did not infringe upon their patent rights. It turned out that I was able to successfully develop a method radically different from theirs. A patent on this method is pending.

It is important that the reader understand another concept about the development of American Toxicology’s hair testing. To be tested in District Court in child custody cases is very significant. We are talking about taking children away from parents. We are talking about people who have already retained legal counsel. There is no room for error. There is also other evidence that corroborates test results that the court sees. If the hair testing was inaccurate, either to the negative or positive, it would not take long for that to be discovered. Simply stated, the testing would not survive.

After over a year of using the hair test in District Court in hundreds of cases, not a single test was impeached or declared inaccurate. It was then that the hair test was introduced into the workplace for pre-employment drug screening. This was in 1993. Since then American Toxicology has continued to perform testing for the District Courts, now into the thousands of cases, and still maintains the same record. Using identical procedures we routinely run workplace hair testing along with court ordered hair testing.

I strongly believe that because American Toxicology hair testing was proven in District Court before being introduced into the workplace, it is ethically a good test and can be used for pre-employment purposes. The argument against using hair testing for pre-employment has always been that someone unknown is taken off the street and a single test determines if they receive a job. There is no corroboration from other sources, no judge, no hearing, no sworn testimonies, or any other evidence able to support a positive result. I believe American Toxicology has overcome this argument by first proving the reliability of its hair test when these elements were available it would be unconscionable for a laboratory to introduce a hair test into the workplace without first proving its reliability.

I hope from what I have presented that those contemplating using hair testing will be convinced that American Toxicology has a reliable hair test. In addition, because drug testing is all that American Toxicology does, we are deeply concerned about employers or agencies that perform drug testing. We will help employer to run its drug testing program safely and smoothly in every way we can. This includes dealing directly with the people who have been tested, if this is desired.

I believe hair testing is the answer to pre-employment drug screening. It gives a cleaner employee population because the window of detection is longer than with urine. American Toxicology uses hair and urine combination, called a profile 100, where the hard drugs are tested in the hair and marijuana is tested in the urine. This is a good profile and has proved to work very well in all aspects of pre-employment drug screening. A urine sample also adds forensic integrity to the tests as well as a greater ability to investigate drug usage. A urine option is also important because some people do not have an adequate hair sample.


For more information visit American Toxicology

Psychemedics' patented hair analysis technology is a proven drug testing method which not only detects if drugs of abuse have been used, but also provides information on the quantity and historic pattern of individual drug use.

This type of information is not available from any other drug screening procedure. Psychemedics' test detects drugs of abuse for the previous several months, while urinalysis will detect use for only the previous 2-3 days for most drugs. Psychemedics' significantly longer testing window results in superior detection rates over urinalysis. In addition, the collection of a hair sample is easier and far less embarrassing than a urine sample.

All initial positives are confirmed using gas chromatography/mass spectrometry (GC/MS). Test results have been consistently upheld in court. In fact, some court systems currently rely on Psychemedics' technology in their probation programs.

The History of Psychemedics' Technology

Psychemedics' patented technology was pioneered in 1977 by Dr. Werner Baumgartner and Annette Baumgartner. Over ten years of research funded by the National Institute of Justice, the Veteran's Administration, the United States Navy and the American Society for Industrial Security on thousands of test subjects have proven that drugs deposited in hair can be measured by radioimmunoassay and ultrasensitive gas chromatograph/mass spectrometry procedures. The effectiveness of hair analysis for drugs of abuse has been documented in more than 500 scientific publications worldwide.

In 1987 Psychemedics became the world's first laboratory to offer a cost effective method for testing using hair rather than body fluids for the detection of drugs of abuse.




Psychemedics' Patents

Psychemedics is the first company to have been awarded both U.S. and foreign patents for the detection of drugs in hair. The first U.S. and European patent covers the universal drug extraction procedure for the detection of drugs in hair specimens.

The second U.S. patent covers the removal of substances which interfere with the immunochemical screening assay for marijuana. The marijuana screening assay is the most challenging scientific problem of hair analysis.

These patents enable Psychemedics to conduct testing far more effectively than other laboratories claiming the ability to detect drugs through hair analysis. More recently, Psychemedics received both European and Japanese patents for its method of hair analysis.

There are companies who have tried to emulate our proprietary process of hair analysis. It is important to remember that all hair testing is not of the same quality.



Hair Testing for a 90-Day Drug
Use History

Hair testing for drugs of abuse is the only drug-testing method available that
provides up to a 90-day drug use history. This makes hair testing from
Employer Solutions an ideal solution for pre-employment and random testing
protocols.

Using FDA-cleared testing reagents, this lab-based test offers the advantages
of easy specimen collection and highly accurate results that meet the same
reference standards as urine testing. In addition, there are no known methods
for sample adulteration (hair washing will not dilute the sample). Because
specimen collection can be directly observed, the risk of adulteration is even
further reduced.1

Fast turnaround of results is also available: Negative results are reported within
24 hours of receipt at the laboratory, and positive results are confirmed using
gas chromatography/mass spectrometry (GC/MS) or gas chromatography/
mass spectrometry/mass spectrometry (GC/MS/MS) within 48 to 72 hours.
Hair testing is also forensically defensible.

When compared with urine specimen testing, hair testing provides up to 2.5
times the number of positives and a longer detection window. In addition,
Quest Diagnostics offers a comprehensive, nationwide collection network and
provides online and CD-ROM-based collection training.

Hair testing can test for the following classes of drugs:



Amphetamines (including Ecstasy)

Cocaine

Marijuana

Opiates

Phencyclidine (PCP)


Six-panel test:





Analyte
Screen Cutoff
Confirmation Cutoff

Amphetamines
Cocaine
Opiates
PCP
THC
THC-COOH


300 pg/mg
300 pg/mg
500 pg/mg
300 pg/mg
N/A
1 pg/mg

300 pg/mg
300 pg/mg
500 pg/mg
300 pg/mg
5 pg/mg
0.1 pg/mg

Convenient non-invasive sample collection

View and print a hair testing brochure.

View FAQs on hair testing.

Take online hair testing training.

For more information on hair testing, contact an
Employer Solutions sales representative
.

1 Not permissible in all states.

For more information visit Quest Diagnostics

Drug Testing Methods

Posted by Kipling M | 12:19 PM | | 0 comments »

DRUG TEST METHODS

There are four basic ways to test a subject for drug use; Urine, hair, saliva and blood. Before continuing, I must say that this text mainly applies to urinalysis. However, I try to cover all drug tests.

It would be helpful if people could somehow find out which test they are getting ahead of time. Though caution must be taken. Asking your boss whether you're getting an instant or lab test or whether the test is a urine, saliva or hair test would imply that you know too much, or seem too curious. There are laws against discriminatory hiring practices and you should know what your rights as an applicant are. Look to your State’s labor laws before going on that next big job hunt.. Most are printed online.

Instant Test Devices

Instant tests enable parents to test their children. This is the most convenient and widely test being used. Employers and court systems use the tests to determine if your specimen screens non-negative and needs further confirmation testing in a lab. These devices can be as simple as a simple one drug dip stick test or as advanced as a cup with the test strip and adulterant check built in. For the stick type of devices, the tester dips the test end of the device into the urine, waits 2-4 minutes, and reads the results. The results will be either negative or non-negative. For the cups, you are given a cup, with the test strip covered by a peal-off type of sticker. Some cups test a portion of the urine while keeping the remainder aside for confirmation at a lab if necessary. Instant devices were never meant to be a device to determine if someone was positive for a banned substance. They should only be used to determine if a substance needs further testing through the lab.

Immunoassay

This procedure is best described in Thein and Landry's word's:
Immunoassays use antigen-antibody interactions to detect illegal substances. Antibodies that bind selectively to certain drugs or drug metabolites are chosen, and the sensitivity and the specificity of this test are only as good as the antibody chosen. The binding is proportional to the amount of drug in the urine and can be detected through enzymes, radioisotopes, or fluorescent compounds. With this technique, very small amounts of drug can be detected in a very small amount of urine, although this test may not differentiate between specific drugs within a class of drugs. Immunoassay has yielded false-positive results with some decongestants and non-steroidal anti-inflammatory drugs. Most are 97-99% accurate and false negatives are more common than false positives. Improper storage and handling are the cause of most faulty instant devices. Don’t store them below 32 degrees or over 90 degrees for any extended period of time.

Gas Chromatography

Gas chromatography uses a separation technique to divide the urine extracts into the component parts. An inert gas carries the urine through chromatographic columns, and the samples are separated by their boiling temperature and by their affinity for the column. Compounds are identified by separation time, called retention time. The retention time is unique and reproducible for each drug in a given chromatographic column.

Gas Chromatography / Mass Spectrometry

The most precise procedure for detection of banned substances is a combination of GC and MS. Gas chromatography/mass spectrometry is a two-step process, where GC separates the sample into its constituent parts, while MS provides the exact molecular identification of the compounds. Compounds are separated by GC and are then introduced, one at a time, into a mass spectrometer. As the sample constituents enter the MS, they are bombarded by electrons, which cause the compound to break up into molecular fragments. The fragmentation pattern is reproducible and characteristic, and is considered the "molecular-fingerprint" of a specific compound. Gas chromatography/mass spectrometry is considered to be the most definitive method for confirming the presence of a drug in the urine and is approximately 100 to 1,000 times more sensitive than TLC. Selective ion monitoring has been used to improve the GC/MS results. This procedure is standard for any and all specimens sent to a lab that have screened non-negative during the screening process.

The GC/MS is typically used to confirm "non-negative" EMIT and immunoassay test results. GC/MS will indicate precisely what chemical is present. This is necessary because the EMIT & immunoassay are only indicators of whether something similar to what's being tested is present. The GC/MS is difficult and more costly, which is why the EMIT and immunoassay screenings are given first. (Hewlett Packard produces the GC/MS equipment, including computer, for about $50-75k depending on options.) Abstinence and substitution are the only ways to defeat the GC/MS test. GC/MS is very precise when done right. However, it's still subject to human error. Inaccurate results are very rare. Most laboratories used today are Department of Health and Human Services Certified. They have been through a rigorous and lengthy testing process and have been found to be below the standard cutoff for errors in testing and/or reporting.

Hair Testing

When THC metabolites are in the blood, they go through the blood vessels in the head, and deposited into the hair. THC metabolites remain in the hair as a permanent record. The hair test costs a little less than a hundred dollars (anywhere from $65-$95) and is not used as often as urinalysis because urinalysis is cheaper (approximately $40-$70). Hair tests are widely used in the casino industry. They cut approximately 50 strands of hair close to the scalp, and send it in to the testing lab where they wash it is washed then liquefied. A hair sample is dissolved in a series of solvents which extract the drug metabolites and then are analyzed via GC/MS. It can take several hours to days just to extract metabolites. Average hair grows 1/2 inch per month. Typically they just use hair one and a half inches from the scalp giving about 90 days of history. It has been rumored that labs can test as far back as 3-6 years. This is false. A lab will not test more than history the 1-1/2 inches of hair will reveal. If a collector splits, for example, 3 inches of hair into two separate samples and submits them as being from different donors, the labs cannot know the specimens are from the same hair. Labs frown on this as it would be considered fraud and is not common practice. The liquid is run through the GC/MS machine, and can detect as little as 1 ng/mL. Psychemedics Corporation has a home collection kit for $69. This home test kit is available if you want to test yourself before applying for a job. Also, parents can test their children.

Beating the hair test is extremely hard, Bleaching or dying your hair is reported to work, but it is very hard on the hair and permanent damage can be expected from such harsh treatments. I imagine you can shave every hair on your body and claim that you're a swimmer, but if you had hair at the interview, and suddenly, after you are informed of an impending hair test, you have no hair; you might be seen as trying to avoid the test.

Currently, the two most prevalent laboratories for hair tests are Psychemedics and Quest Diagnostics. Approximately 90% of all hair tests sent to laboratories are sent to one of these two powerhouses. Omega Laboratories and American Toxicology are the other contenders in the hair testing market.

Immunoassay

From Wikipedia, the free encyclopedia

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An immunoassay is a biochemical test that measures the concentration of a substance in a biological liquid, typically serum or urine, using the reaction of an antibody or antibodies to its antigen. The assay takes advantage of the specific binding of an antibody to its antigen. Monoclonal antibodies are often used as they only usually bind to one site of a particular molecule, and therefore provide a more specific and accurate test, which is less easily confused by the presence of other molecules. The antibodies picked must have a high affinity for the antigen (if there is antigen available, a very high proportion of it must bind to the antibody).

Both the presence of antigen or antibodies can be measured. For instance, when seeking to detect the presence of an infection the concentration of antibody specific to that particular pathogen is measured. For measuring hormones such as insulin, the insulin acts as the antigen.

For numerical results, the response of the fluid being measured must be compared to standards of a known concentration. This is usually done through the plotting of a standard curve on a graph, the position of the curve at response of the unknown is then examined, and so the quantity of the unknown found.

Detecting the quantity of antibody or antigen can be achieved by a variety of methods. One of the most common is to label either the antigen or antibody. The label may consist of an enzyme (see enzyme immunoassay (EIA)), colloidal gold (lateral flow assays), radioisotopes such as I-125 Radioimmunoassay (RIA), magnetic labels (magnetic immunoassay - MIA) or fluorescence. Other techniques include agglutination, nephelometry, turbidimetry and Western Blot.

Immunoassays have a particularly important role in the diagnosis of many Infectious Diseases, including HIV. Immunoassays are just one type of diagnostic HIV test.

[edit] Types

Immunoassays can be divided into those that involve labelled reagents and those which involve non-labelled reagents. Those which involve labelled reagents are divided into homogenous and heterogeneous (which require an extra step to remove unbound antibody or antigen from the site, usually using a solid phase reagent) immunoassays. Heterogeneous immunoassays can be competitive or non-competitive.

  • In a competitive immunoassay, the antigen in the unknown sample competes with labeled antigen to bind with antibodies. The amount of labeled antigen bound to the antibody site is then measured. In this method, the response will be inversely proportional to the concentration of antigen in the unknown. This is because the greater the response, the less antigen in the unknown was available to compete with the labeled antigen.
  • In noncompetitive immunoassays, also referred to as the "sandwich assay," antigen in the unknown is bound to the antibody site, then labeled antibody is bound to the antigen. The amount of labeled antibody on the site is then measured. Unlike the competitive method, the results of the noncompetitive method will be directly proportional to the concentration of the antigen. This is because labeled antibody will not bind if the antigen is not present in the unknown sample.

Because homogeneous assays do not require this step, they are typically faster and easier to perform.


[edit] See also

[edit] External links

See also Chapter 5 and 6 in the book "Bioanalytical Chemistry" by Susan R. Mikkelsen

Gas chromatography-mass spectrometry

From Wikipedia, the free encyclopedia

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Example of a GC-MS

Gas chromatography-mass spectrometry (GC-MS) is a method that combines the features of gas-liquid chromatography and mass spectrometry to identify different substances within a test sample. Applications of GC-MS include drug detection, fire investigation, environmental analysis, explosives investigation, and identification of unknown samples. GC/MS can also be used in airport security to detect substances in luggage or on human beings. Additionally, it can identify trace elements in materials that were previously thought to have disintegrated beyond identification.

The GC-MS has been widely heralded as a "gold standard" for forensic substance identification because it is used to perform a specific test. A specific test positively identifies the actual presence of a particular substance in a given sample. A non-specific test merely indicates that a substance falls into a category of substances. Although a non-specific test could statistically suggest the identity of the substance, this could lead to false positive identification.

Contents

[hide]

[edit] History

The use of a mass spectrometer as the detector in gas chromatography was developed during the 1950s by Roland Gohlke and Fred McLafferty.[1][2] These sensitive devices were bulky, fragile, and originally limited to laboratory settings. The development of affordable and miniaturized computers has helped in the simplification of the use of this instrument, as well as allowed great improvements in the amount of time it takes to analyze a sample. In 1996 the top-of-the-line high-speed GC-MS units completed analysis of fire accelerants in less than 90 seconds, whereas first-generation GC/MS would have required at least 16 minutes.[citation needed] This has led to their widespread adoption in a number of fields.

[edit] Instrumentation

The insides of the GC-MS, with the column of the gas chromatograph in the oven on the right.

The GC-MS is composed of two major building blocks: the gas chromatograph and the mass spectrometer. The gas chromatograph utilizes a capillary column which depends on the column's dimensions (length, diameter, film thickness) as well as the phase properties (e.g. 5% phenyl polysiloxane). The difference in the chemical properties between different molecules in a mixture will separate the molecules as the sample travels the length of the column. The molecules take different amounts of time (called the retention time) to come out of (elute from) the gas chromatograph, and this allows the mass spectrometer downstream to capture, ionize, accelerate, deflect, and detect the ionized molecules separately. The mass spectrometer does this by breaking each molecule into ionized fragments and detecting these fragments using their mass to charge ratio.

GC-MS schematic

These two components, used together, allow a much finer degree of substance identification than either unit used separately. It is not possible to make an accurate identification of a particular molecule by gas chromatography or mass spectrometry alone. The mass spectrometry process normally requires a very pure sample while gas chromatography using a traditional detector (e.g. Flame Ionization Detector) detects multiple molecules that happen to take the same amount of time to travel through the column (i.e. have the same retention time) which results in two or more molecules to co-elute. Sometimes two different molecules can also have a similar pattern of ionized fragments in a mass spectrometer (mass spectrum). Combining the two processes makes it extremely unlikely that two different molecules will behave in the same way in both a gas chromatograph and a mass spectrometer. Therefore when an identifying mass spectrum appears at a characteristic retention time in a GC-MS analysis, it typically lends to increased certainty that the analyte of interest is in the sample.

[edit] Split/Splitless GC-MS inlets

Samples are introduced to the column via an inlet. This inlet is typically injection through a septum. Once in the inlet, the heated chamber acts to volatilize the sample. In a split system, a constant flow of carrier gas moves through the inlet. A portion of the carrier gas flow acts to transport the sample into the column. Another portion of the carrier gas flow gets directed to purge the inlet of any sample following injection (septum purge). Yet another portion of the flow is directed through the split vent in a set ratio known as the split ratio. In a splitless system, the advantage is that a larger amount of sample is introduced to the column. However, a split system is preferred when the detector is sensitive to trace amounts of analyte and there is concern about overloading the column.

[edit] Purge and Trap GC-MS

For the analysis of volatile compounds a Purge and Trap (P&T) concentrator system may be used to introduce samples. The target analytes are extracted and mixed with water and introduced into an airtight chamber. An inert gas such as Nitrogen (N2) is bubbled through the water; this is known as purging. The volatile compounds move into the headspace above the water and are drawn along a pressure gradient (caused by the introduction of the purge gas) out of the chamber. The volatile compounds are drawn along a heated line onto a 'trap'. the trap is a column of adsorbent material at ambient temperature that holds the compounds by returning them to the liquid phase. The trap is then heated and the sample compounds are introduced to the GC-MS column via a volatiles interface, which is a split inlet system. P&T GC-MS is particularly suited to volatile organic compounds (VOCs) and BTEX compounds (aromatic compounds associated with petroleum).[3]

[edit] Types of Mass Spectrometer Detectors

The most common type of mass spectrometer (MS) associated with a gas chromatograph (GC) is the quadrupole mass spectrometer, sometimes referred to by the Hewlett-Packard (now Agilent) trade name "Mass Selective Detector" (MSD). Another relatively common detector is the ion trap mass spectrometer. Additionally one may find a magnetic sector mass spectrometer, however these particular instruments are expensive and bulky and not typically found in high-throughput service laboratories. Other detectors may be encountered such as time of flight (TOF), tandem quadrupoles (MS-MS) (see below), or in the case of an ion trap MSn where n indicates the number mass spectrometry stages.

[edit] Analysis

A mass spectrometer is typically utilized in one of two ways: Full Scan or Selective Ion Monitoring (SIM). The typical GC/MS instrument is capable of performing both functions either individually or concomitantly, depending on the setup of the particular instrument.

[edit] Full scan MS

When collecting data in the full scan mode, a target range of mass fragments is determined and put into the instrument's method. An example of a typical broad range of mass fragments to monitor would be m/z 50 to m/z 400. The determination of what range to use is largely dictated by what one anticipates being in the sample while being cognizant of the solvent and other possible interferences. A MS should not be set to look for mass fragments too low or else one may detect air (found as m/z 28 due to nitrogen), carbon dioxide (m/z 44) or other possible interferences. Additionally if one is to use a large scan range then sensitivity of the instrument is decreased due to performing fewer scans per second since each scan will have to detect a wide range of mass fragments.

Full scan is useful in determining unknown compounds in a sample. It provides more information than SIM when it comes to confirming or resolving compounds in a sample. During instrument method development it may be common to first analyze test solutions in full scan mode to determine the retention time and the mass fragment fingerprint before moving to a SIM instrument method.

[edit] Selected ion monitoring

In selected ion monitoring (SIM) certain ion fragments are entered into the instrument method and only those mass fragments are detected by the mass spectrometer. The advantages of SIM are that the detection limit is lower since the instrument is only looking at a small number of fragments (e.g. three fragments) during each scan. More scans can take place each second. Since only a few mass fragments of interest are being monitored, matrix interferences are typically lower. To additionally confirm the likelihood of a potentially positive result, it is relatively important to be sure that the ion ratios of the various mass fragments are comparable to a known reference standard.

[edit] Types of Ionization

After the molecules travel the length of the column, pass through the transfer line and enter into the mass spectrometer they are ionized by various methods with typically only one method being used at any given time. Once the sample is fragmented it will then be detected, usually by an electron multiplier diode, which essentially turns the ionized mass fragment into an electrical signal that is then detected.

The ionization technique chosen is independent of using Full Scan or SIM.

[edit] Electron Ionization

By far the most common and perhaps standard form of ionization is electron ionization (EI). The molecules enter into the MS (the source is a quadrupole or the ion trap itself in an ion trap MS) where they are bombarded with free electrons emitted from a filament, not much unlike the filament one would find in a standard light bulb. The electrons bombard the molecules, causing the molecule to fragment in a characteristic and reproducible way. This "hard ionization" technique results in the creation of more fragments of low mass to charge ratio (m/z) and few, if any, molecules approaching the molecular mass unit. Hard ionization is considered by mass spectroscopists as the employ of molecular electron bombardment, whereas "soft ionization" is charge by molecular collision with an introduced gas. The molecular fragmentation pattern is dependant upon the electron energy applied to the system, typically 70eV (electron Volts). The use of 70eV facilitates comparison of generated spectra with National Institute of Standard (NIST-USA) library of spectra applying algorithmic matching programs and the use of methods of analysis written by many method standardization agencies.

[edit] Chemical Ionization

In chemical ionization a reagent gas, typically methane or ammonia is introduced into the mass spectrometer. Depending on the technique (positive CI or negative CI) chosen, this reagent gas will interact with the electrons and analyte and cause a 'soft' ionization of the molecule of interest. A softer ionization fragments the molecule to a lower degree than the hard ionization of EI. One of the main benefits of using chemical ionization is that a mass fragment closely corresponding to the molecular weight of the analyte of interest is produced.

Positive Chemical Ionization

In Positive Chemical Ionization (PCI) the reagent gas interacts with the target molecule, most often with a proton exchange. This produces the species in relatively high amounts.

Negative Chemical Ionization

In Negative Chemical Ionization (NCI) the reagent gas decreases the impact of the free electrons on the target analyte. This decreased energy typically leaves the fragment in great supply.

The primary goal of instrument analysis is to quantify an amount of substance. This is done by comparing the relative concentrations among the atomic masses in the generated spectrum. Two kinds of analysis are possible, comparative and original. Comparative analysis essentially compares the given spectrum to a spectrum library to see if its characteristics are present for some sample in the library. This is best performed by a computer because there are a myriad of visual distortions that can take place due to variations in scale. Computers can also simultaneously correlate more data (such as the retention times identified by GC), to more accurately relate certain data.

Another method of analysis measures the peaks in relation to one another. In this method, the tallest peak is assigned 100% of the value, and the other peaks being assigned proportionate values. All values above 3% are assigned. The total mass of the unknown compound is normally indicated by the parent peak. The value of this parent peak can be used to fit with a chemical formula containing the various elements which are believed to be in the compound. The isotope pattern in the spectrum, which is unique for elements that have many isotopes, can also be used to identify the various elements present. Once a chemical formula has been matched to the spectrum, the molecular structure and bonding can be identified, and must be consistent with the characteristics recorded by GC/MS. Typically, this identification done automatically by programs which come with the instrument, given a list of the elements which could be present in the sample.

A “full spectrum” analysis considers all the “peaks” within a spectrum. Conversely, selective ion monitoring (SIM) only monitors selected peaks associated with a specific substance. This is done on the assumption that at a given retention time, a set of ions is characteristic of a certain compound. This is a fast and efficient analysis, especially if the analyst has previous information about a sample or is only looking for a few specific substances. When the amount of information collected about the ions in a given gas chromatographic peak decreases, the sensitivity of the analysis increases. So, SIM analysis allows for a smaller quantity of a compound to be detected and measured, but the degree of certainty about the identity of that compound is reduced.

[edit] GC-MS/MS

When a second phase of mass fragmentation is added, for example using a second quadrupole in a quadrupole instrument, it is called MS/MS or Tandem MS. Tandem mass spectrometry (MS/MS) is a more powerful technique to quantitate low levels of target compounds in the presence of a high sample matrix background.

The first quadrupole (Q1) is connected with a collision cell (q2) and another quadrupole (Q3). Both quadrupoles can be used in scanning or static mode, depending on the type of MS/MS analysis being performed. Types of analysis include product ion scan, precursor ion scan, Single Reaction Monitoring (SRM) and Multiple Reaction Monitoring (MRM) and Neutral Loss Scan. For example: When Q1 is in static mode (looking at one mass only as in SIM), and Q3 is in scanning mode, one obtains a so-called product ion spectrum (also called "daughter spectrum"). From this spectrum, one can select a prominent product ion which can be the product ion for the chosen precursor ion. The pair is called a "transition" and forms the basis for SRM (MRM is sometimes used as term). SRM is highly specific and virtually eliminates matrix background.

[edit] Applications

[edit] Environmental Monitoring and Cleanup

GC-MS is becoming the tool of choice for tracking organic pollutants in the environment. The cost of GC-MS equipment has decreased significantly, and the reliability has increased at the same time, which has contributed to its increased adoption in environmental studies. There are some compounds for which GC-MS is not sufficiently sensitive, including certain pesticides and herbicides, but for most organic analysis of environmental samples, including many major classes of pesticides, it is very sensitive and effective.

[edit] Criminal Forensics

GC-MS can analyze the particles from a human body in order to help link a criminal to a crime. The analysis of fire debris using GC-MS is well established, and there is even an established American Society for Testing Materials (ASTM) standard for fire debris analysis. GCMS/MS is especially useful here as samples often contain very complex matrices and results, used in court, need to be highly accurate.

[edit] Law Enforcement

GC-MS is increasingly used for detection of illegal narcotics, and may eventually supplant drug-sniffing dogs.[1] It is also commonly used in forensic toxicology to find drugs and/or poisons in biological specimens of suspects, victims, or the deceased.

[edit] Security

A post-September 11 development, explosive detection systems have become a part of all US airports. These systems run on a host of technologies, many of them based on GC-MS. There are only three manufacturers certified by the FAA to provide these systems,[citation needed] one of which is Thermo Detection (formerly Thermedics), which produces the EGIS, a GC-MS-based line of explosives detectors. The other two manufacturers are Barringer Technologies, now owned by Smith's Detection Systems and Ion Track Instruments, part of General Electric Infrastructure Security Systems.

[edit] Food, Beverage and Perfume Analysis

Foods and beverages contain numerous aromatic compounds, some naturally present in the raw materials and some forming during processing. GC-MS is extensively used for the analysis of these compounds which include esters, fatty acids, alcohols, aldehydes, terpenes etc. It is also used to detect and measure contaminants from spoilage or adulteration which may be harmful and which is often controlled by governmental agencies, for example pesticides.

[edit] Astrochemistry

Several GC-MS have left earth. Two were brought to Mars by the Viking program.[4] Venera 11 and 12 and Pioneer Venus analysed the atmosphere of Venus with GC-MS.[5] The Huygens probe of the Cassini-Huygens mission landed one GC-MS on Saturn's largest moon, Titan.[6] The material in the comet 67P/Churyumov-Gerasimenko will be analysed by the Rosetta mission with a chiral GC-MS in 2014. [7]

[edit] Medicine

In combination with isotopic labeling of metabolic compounds, the GC-MS is used for determining metabolic activity. Most applications are based on the use of 13C as the labeling and the measurement of 13C/12C ratios with an isotope ratio mass spectrometer (IRMS); an MS with a detector designed to measure a few select ions and return values as ratios.

[edit] See also

[edit] References

  1. ^ Gohlke, R. S. (1959). "Time-of-Flight Mass Spectrometry and Gas-Liquid Partition Chromatography". Analytical Chemistry 31: 535. doi:10.1021/ac50164a024.
  2. ^ Gohlke, R (1993). "Early gas chromatography/mass spectrometry". Journal of the American Society for Mass Spectrometry 4: 367. doi:10.1016/1044-0305(93)85001-E.
  3. ^ "Optimizing the Analysis of Volatile Organic Compounds - Technical Guide" Restek Corporation, Lit. Cat. 59887A
  4. ^ The Development of the Viking GCMS
  5. ^ V. A. Krasnopolsky, V. A. Parshev (1981). "Chemical composition of the atmosphere of Venus". Nature 292: 610–613. doi:10.1038/292610a0.
  6. ^ H. B. Niemann, S. K. Atreya, S. J. Bauer, G. R. Carignan, J. E. Demick, R. L. Frost, D. Gautier, J. A. Haberman, D. N. Harpold, D. M. Hunten, G. Israel, J. I. Lunine, W. T. Kasprzak, T. C. Owen, M. Paulkovich, F. Raulin, E. Raaen, S. H. Way (2005). "The abundances of constituents of Titan’s atmosphere from the GCMS instrument on the Huygens probe". Nature 438: 77–9–784. doi:10.1038/nature04122.
  7. ^ Goesmann F, Rosenbauer H, Roll R, Bohnhardt H (2005). "COSAC onboard Rosetta: A bioastronomy experiment for the short-period comet 67P/Churyumov-Gerasimenko". Astrobiology 5 (5): 622–631. doi:10.1089/ast.2005.5.622.

[edit] Bibliography

  • Robert P., Dr Adams (2007). Identification of Essential Oil Components By Gas Chromatography/Mass Spectrometry. Allured Pub Corp. ISBN 1-932633-21-9.
  • Adlard, E. R.; Handley, Alan J. (2001). Gas chromatographic techniques and applications. London: Sheffield Academic. ISBN 0-8493-0521-7.
  • Eugene F. Barry; Grob, Robert Lee (2004). Modern practice of gas chromatography. New York: Wiley-Interscience. ISBN 0-471-22983-0.
  • Eiceman, G.A. (2000). Gas Chromatography. In R.A. Meyers (Ed.), Encyclopedia of Analytical Chemistry: Applications, Theory, and Instrumentation, pp. 10627. Chichester: Wiley. ISBN 0-471-97670-9
  • Giannelli, Paul C. and Imwinkelried, Edward J. (1999). Drug Identification: Gas Chromatography. In Scientific Evidence 2, pp. 362. Charlottesville: Lexis Law Publishing. ISBN 0-327-04985-5.
  • McEwen, Charles N.; Kitson, Fulton G.; Larsen, Barbara Seliger (1996). Gas chromatography and mass spectrometry: a practical guide. Boston: Academic Press. ISBN 0-12-483385-3.
  • McMaster, Christopher; McMaster, Marvin C. (1998). GC/MS: a practical user's guide. New York: Wiley. ISBN 0-471-24826-6.
  • Message, Gordon M. (1984). Practical aspects of gas chromatography/mass spectrometry. New York: Wiley. ISBN 0-471-06277-4.
  • Niessen, W. M. A. (2001). Current practice of gas chromatography--mass spectrometry. New York, N.Y: Marcel Dekker. ISBN 0-8247-0473-8.
  • Weber, Armin; Maurer, Hans W.; Pfleger, Karl (2007). Mass Spectral and GC Data of Drugs, Poisons, Pesticides, Pollutants and Their Metabolites. Weinheim: Wiley-VCH. ISBN 3-527-31538-1.

[edit] External links

Gas-liquid chromatography

From Wikipedia, the free encyclopedia

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Gas-liquid chromatography
Gaschromatograph.jpg
A gas chromatograph with a headspace sampler
Acronym GLC, GC
Classification chromatography
Analytes organic
inorganic
must be volatile
Manufacturers Agilent (a spin-off of Hewlett-Packard)
LECO Corporation
PerkinElmer
Shimadzu
Thermo Electron Corporation
Varian, Inc.
Alpha MOS - Perichrom
Other Techniques
Related Thin layer chromatography
High performance liquid chromatography
Hyphenated Gas chromatography-mass spectrometry

Gas-liquid chromatography (GLC), or simply gas chromatography (GC), is a common type of chromatography used in analytic chemistry for separating and analyzing compounds that can be vaporized without decomposition. Typical uses of GC include testing the purity of a particular substance, or separating the different components of a mixture (the relative amounts of such components can also be determined). In some situations, GC may help in identifying a compound. In preparative chromatography, GC can be used to prepare pure compounds from a mixture.[1]

In gas chromatography, the moving phase (or "mobile phase") is a carrier gas, usually an inert gas such as helium or an unreactive gas such as nitrogen. The stationary phase is a microscopic layer of liquid or polymer on an inert solid support, inside a piece of glass or metal tubing called a column (an homage to the fractionating column used in distillation). The instrument used to perform gas chromatography is called a gas chromatograph (or "aerograph", "gas separator").

The gaseous compounds being analyzed interact with the walls of the column, which is coated with different stationary phases. This causes each compound to elute at a different time, known as the retention time of the compound. The comparison of retention times is what gives GC its analytical usefulness.

Gas chromatography is in principle similar to column chromatography (as well as other forms of chromatography, such as HPLC, TLC), but has several notable differences. Firstly, the process of separating the compounds in a mixture is carried out between a liquid stationary phase and a gas moving phase, whereas in column chromatography the stationary phase is a solid and the moving phase is a liquid. (Hence the full name of the procedure is "Gas-liquid chromatography", referring to the mobile and stationary phases, respectively.) Secondly, the column through which the gas phase passes is located in an oven where the temperature of the gas can be controlled, whereas column chromatography (typically) has no such temperature control. Thirdly, the concentration of a compound in the gas phase is solely a function of the vapor pressure of the gas.[1]

Gas chromatography is also similar to fractional distillation, since both processes separate the components of a mixture primarily based on boiling point (or vapor pressure) differences. However, fractional distillation is typically used to separate components of a mixture on a large scale, whereas GC can be used on a much smaller scale (i.e. microscale).[1]

Gas chromatography is also sometimes known as vapor-phase chromatography (VPC), or gas-liquid partition chromatography (GLPC). These alternative names, as well as their respective abbreviations, are frequently found in scientific literature. Strictly speaking, GLPC is the most correct terminology, and is thus preferred by many authors.[1]

Contents

[hide]

[edit] History

Chromatography dates to 1903 in the work of the Russian scientist, Mikhail Semenovich Tswett. German graduate student Fritz Prior developed solid state gas chromatography in 1947. Archer John Porter Martin, who was awarded the Nobel Prize for his work in developing liquid-liquid (1941) and paper (1944) chromatography, laid the foundation for the development of gas chromatography and later produced liquid-gas chromatography (1950).

[edit] GC analysis

A gas chromatograph is a chemical analysis instrument for separating chemicals in a complex sample. A gas chromatograph uses a flow-through narrow tube known as the column, through which different chemical constituents of a sample pass in a gas stream (carrier gas, mobile phase) at different rates depending on their various chemical and physical properties and their interaction with a specific column filling, called the stationary phase. As the chemicals exit the end of the column, they are detected and identified electronically. The function of the stationary phase in the column is to separate different components, causing each one to exit the column at a different time (retention time). Other parameters that can be used to alter the order or time of retention are the carrier gas flow rate, and the temperature.

In a GC analysis, a known volume of gaseous or liquid analyte is injected into the "entrance" (head) of the column, usually using a microsyringe (or, solid phase microextraction fibers, or a gas source switching system). As the carrier gas sweeps the analyte molecules through the column, this motion is inhibited by the adsorption of the analyte molecules either onto the column walls or onto packing materials in the column. The rate at which the molecules progress along the column depends on the strength of adsorption, which in turn depends on the type of molecule and on the stationary phase materials. Since each type of molecule has a different rate of progression, the various components of the analyte mixture are separated as they progress along the column and reach the end of the column at different times (retention time). A detector is used to monitor the outlet stream from the column; thus, the time at which each component reaches the outlet and the amount of that component can be determined. Generally, substances are identified (qualitatively) by the order in which they emerge (elute) from the column and by the retention time of the analyte in the column.

[edit] Physical components

Diagram of a gas chromatograph.

[edit] Autosamplers

The autosampler provides the means to introduce a sample automatically into the inlets. Manual insertion of the sample is possible but is no longer common. Automatic insertion provides better reproducibility and time-optimization.

Different kinds of autosamplers exist. Autosamplers can be classified in relation to sample capacity (auto-injectors vs. autosamplers, where auto-injectors can work a small number of samples), to robotic technologies (XYZ robot vs. rotating robot – the most common), or to analysis:

Traditionally autosampler manufacturers are different from GC manufacturers and currently no GC manufacturer offers a complete range of autosamplers. Historically, the countries most active in autosampler technology development are the United States, Italy and Switzerland.

[edit] Inlets

The column inlet (or injector) provides the means to introduce a sample into a continuous flow of carrier gas. The inlet is a piece of hardware attached to the column head.

Common inlet types are:

  • S/SL (Split/Splitless) injector; a sample is introduced into a heated small chamber via a syringe through a septum - the heat facilitates volatilization of the sample and sample matrix. The carrier gas then either sweeps the entirety (splitless mode) or a portion (split mode) of the sample into the column. In split mode, a part of the sample/carrier gas mixture in the injection chamber is exhausted through the split vent. Split injection is preferred when working with samples with high analyte concentrations (>0.1%) whereas splitless injection is best suited for trace analysis with low amounts of analytes. (<0.01%)
  • On-column inlet; the sample is here introduced in its entirety without heat.
  • PTV injector; Temperature-programmed sample introduction was first described by Vogt in 1979. Originally Vogt developed the technique as a method for the introduction of large sample volumes (up to 250 µL) in capillary GC. Vogt introduced the sample into the liner at a controlled injection rate. The temperature of the liner was chosen slightly below the boiling point of the solvent. The low-boiling solvent was continuously evaporated and vented through the split line. Based on this technique, Poy developed the Programmed Temperature Vaporising injector; PTV. By introducing the sample at a low initial liner temperature many of the disadvantages of the classic hot injection techniques could be circumvented.
  • Gas source inlet or gas switching valve; gaseous samples in collection bottles are connected to what is most commonly a six-port switching valve. The carrier gas flow is not interrupted while a sample can be expanded into a previously evacuated sample loop. Upon switching, the contents of the sample loop are inserted into the carrier gas stream.
  • P/T (Purge-and-Trap) system; An inert gas is bubbled through an aqueous sample causing insoluble volatile chemicals to be purged from the matrix. The volatiles are 'trapped' on an absorbent column (known as a trap or concentrator) at ambient temperature. The trap is then heated and the volatiles are directed into the carrier gas stream. Samples requiring preconcentration or purification can be introduced via such a system, usually hooked up to the S/SL port.
  • SPME (solid phase microextraction) offers a convenient, low-cost alternative to P/T systems with the versatility of a syringe and simple use of the S/SL port.

[edit] Columns

Two types of columns are used in GC:

  • Packed columns are 1.5 - 10 m in length and have an internal diameter of 2 - 4 mm. The tubing is usually made of stainless steel or glass and contains a packing of finely divided, inert, solid support material (eg. diatomaceous earth) that is coated with a liquid or solid stationary phase. The nature of the coating material determines what type of materials will be most strongly adsorbed. Thus numerous columns are available that are designed to separate specific types of compounds.
  • Capillary columns have a very small internal diameter, on the order of a few tenths of millimeters, and lengths between 25-60 meters are common. The inner column walls are coated with the active materials (WCOT columns), some columns are quasi solid filled with many parallel micropores (PLOT columns). Most capillary columns are made of fused-silica with a polyimide outer coating. These columns are flexible, so a very long column can be wound into a small coil.
  • New developments are sought where stationary phase incompatibilities lead to geometric solutions of parallel columns within one column. Among these new developments are:
    • Internally heated microFAST columns, where two columns, an internal heating wire and a temperature sensor are combined within a common column sheath (microFAST);
    • Micropacked columns (1/16" OD) are column-in-column packed columns where the outer column space has a packing different from the inner column space, thus providing the separation behaviour of two columns in one. They can easily fit to inlets and detectors of a capillary column instrument.

The temperature-dependence of molecular adsorption and of the rate of progression along the column necessitates a careful control of the column temperature to within a few tenths of a degree for precise work. Reducing the temperature produces the greatest level of separation, but can result in very long elution times. For some cases temperature is ramped either continuously or in steps to provide the desired separation. This is referred to as a temperature program. Electronic pressure control can also be used to modify flow rate during the analysis, aiding in faster run times while keeping acceptable levels of separation.

The choice of carrier gas (mobile phase) is important, with hydrogen being the most efficient and providing the best separation. However, helium has a larger range of flowrates that are comparable to hydrogen in efficiency, with the added advantage that helium is non-flammable, and works with a greater number of detectors. Therefore, helium is the most common carrier gas used.

[edit] Detectors

A number of detectors are used in gas chromatography. The most common are the flame ionization detector (FID) and the thermal conductivity detector (TCD). Both are sensitive to a wide range of components, and both work over a wide range of concentrations. While TCDs are essentially universal and can be used to detect any component other than the carrier gas (as long as their thermal conductivities are different from that of the carrier gas, at detector temperature), FIDs are sensitive primarily to hydrocarbons, and are more sensitive to them than TCD. However, an FID cannot detect water. Both detectors are also quite robust. Since TCD is non-destructive, it can be operated in-series before an FID (destructive), thus providing complementary detection of the same analytes.

Other detectors are sensitive only to specific types of substances, or work well only in narrower ranges of concentrations. They include:

Some gas chromatographs are connected to a mass spectrometer which acts as the detector. The combination is known as GC-MS. Some GC-MS are connected to an NMR spectrometer which acts as a back up detector. This combination is known as GC-MS-NMR. Some GC-MS-NMR are connected to an infrared spectrophotometer which acts as a back up detector. This combination is known as GC-MS-NMR-IR. It must, however, be stressed this is very rare as most analyses needed can be concluded via purely GC-MS.

[edit] Methods

The method is the collection of conditions in which the GC operates for a given analysis. Method development is the process of determining what conditions are adequate and/or ideal for the analysis required.

Conditions which can be varied to accommodate a required analysis include inlet temperature, detector temperature, column temperature and temperature program, carrier gas and carrier gas flow rates, the column's stationary phase, diameter and length, inlet type and flow rates, sample size and injection technique. Depending on the detector(s) (see below) installed on the GC, there may be a number of detector conditions that can also be varied. Some GCs also include valves which can change the route of sample and carrier flow. The timing of the opening and closing of these valves can be important to method development.

GeoStrataEclipse.jpg

This image above shows the interior of a GeoStrata Technologies Eclipse Gas Chromatograph that runs continuously in three minute cycles. Two valves are used to switch the test gas into the sample loop. After filling the sample loop with test gas, the valves are switched again applying carrier gas pressure to the sample loop and forcing the sample through the Column for separation.

[edit] Carrier gas selection and flow rates

Typical carrier gases include helium, nitrogen, argon, hydrogen and air. Which gas to use is usually determined by the detector being used, for example, a DID requires helium as the carrier gas. When analyzing gas samples, however, the carrier is sometimes selected based on the sample's matrix, for example, when analyzing a mixture in argon, an argon carrier is preferred, because the argon in the sample does not show up on the chromatogram. Safety and availability can also influence carrier selection, for example, hydrogen is flammable, and high-purity helium can be difficult to obtain in some areas of the world. (See: Helium--occurrence and production.)

The purity of the carrier gas is also frequently determined by the detector, though the level of sensitivity needed can also play a significant role. Typically, purities of 99.995% or higher are used. Trade names for typical purities include "Zero Grade," "Ultra-High Purity (UHP) Grade," "4.5 Grade" and "5.0 Grade."

The carrier gas flow rate affects the analysis in the same way that temperature does (see above). The higher the flow rate the faster the analysis, but the lower the separation between analytes. Selecting the flow rate is therefore the same compromise between the level of separation and length of analysis as selecting the column temperature.

With GCs made before the 1990s, carrier flow rate was controlled indirectly by controlling the carrier inlet pressure, or "column head pressure." The actual flow rate was measured at the outlet of the column or the detector with an electronic flow meter, or a bubble flow meter, and could be an involved, time consuming, and frustrating process. The pressure setting was not able to be varied during the run, and thus the flow was essentially constant during the analysis. The relation between flow rate and inlet pressure is calculated with Poiseuille's equation for compressible fluids.

Many modern GCs, however, electronically measure the flow rate, and electronically control the carrier gas pressure to set the flow rate. Consequently, carrier pressures and flow rates can be adjusted during the run, creating pressure/flow programs similar to temperature programs.

[edit] Inlet types and flow rates

The choice of inlet type and injection technique depends on if the sample is in liquid, gas, adsorbed, or solid form, and on whether a solvent matrix is present that has to be vaporized. Dissolved samples can be introduced directly onto the column via a COC injector, if the conditions are well known; if a solvent matrix has to be vaporized and partially removed, a S/SL injector is used (most common injection technique); gaseous samples (e.g., air cylinders) are usually injected using a gas switching valve system; adsorbed samples (e.g., on adsorbent tubes) are introduced using either an external (on-line or off-line) desorption apparatus such as a purge-and-trap system, or are desorbed in the S/SL injector (SPME applications).

[edit] Sample size and injection technique

[edit] Sample injection

The rule of ten in gas chromatography

The real chromatographic analysis starts with the introduction of the sample onto the column. The development of capillary gas chromatography resulted in many practical problems with the injection technique. The technique of on-column injection, often used with packed columns, is usually not possible with capillary columns. The injection system, in the capillary gas chromatograph, should fulfil the following two requirements:

  1. The amount injected should not overload the column.
  2. The width of the injected plug should be small compared to the spreading due to the chromatographic process. Failure to comply with this requirement will reduce the separation capability of the column. As a general rule, the volume injected, Vinj, and the volume of the detector cell, Vdet, should be about 1/10 of the volume occupied by the portion of sample containing the molecules of interest (analytes) when they exit the column.

Some general requirements, which a good injection technique should fulfill, are:

  • It should be possible to obtain the column’s optimum separation efficiency.
  • It should allow accurate and reproducible injections of small amounts of representative samples.
  • It should induce no change in sample composition. It should not exhibit discrimination based on differences in boiling point, polarity, concentration or thermal/catalytic stability.
  • It should be applicable for trace analysis as well as for undiluted samples.

'''Select dimensions of column for corresponding samples and GC System[Limit Temp]''[Dec-2009]'

[edit] Column selection

[edit] Column temperature and temperature program

A gas chromatography oven, open to show a capillary column

The column(s) in a GC are contained in an oven, the temperature of which is precisely controlled electronically. (When discussing the "temperature of the column," an analyst is technically referring to the temperature of the column oven. The distinction, however, is not important and will not subsequently be made in this article.)

The rate at which a sample passes through the column is directly proportional to the temperature of the column. The higher the column temperature, the faster the sample moves through the column. However, the faster a sample moves through the column, the less it interacts with the stationary phase, and the less the analytes are separated.

In general, the column temperature is selected to compromise between the length of the analysis and the level of separation.

A method which holds the column at the same temperature for the entire analysis is called "isothermal." Most methods, however, increase the column temperature during the analysis, the initial temperature, rate of temperature increase (the temperature "ramp") and final temperature is called the "temperature program."

A temperature program allows analytes that elute early in the analysis to separate adequately, while shortening the time it takes for late-eluting analytes to pass through the column.

[edit] Data reduction and analysis

Qualitative analysis:

Generally chromatographic data is presented as a graph of detector response (y-axis) against retention time (x-axis), which is called a chromatogram. This provides a spectrum of peaks for a sample representing the analytes present in a sample eluting from the column at different times. Retention time can be used to identify analytes if the method conditions are constant. Also, the pattern of peaks will be constant for a sample under constant conditions and can identify complex mixtures of analytes. In most modern applications however the GC is connected to a mass spectrometer or similar detector that is capable of identifying the analytes represented by the peaks.

Quantitive analysis:

The area under a peak is proportional to the amount of analyte present in the chromatogram. By calculating the area of the peak using the mathematical function of integration, the concentration of an analyte in the original sample can be determined. Concentration can be calculated using a calibration curve created by finding the response for a series of concentrations of analyte, or by determining the relative response factor of an analyte. The relative response factor is the expected ratio of an analyte to an internal standard (or external standard) and is calculated by finding the response of a known amount of analyte and a constant amount of internal standard (a chemical added to the sample at a constant concentration, with a distinct retention time to the analyte).

In most modern GC-MS systems, computer software is used to draw and integrate peaks, and match MS spectra to library spectra.

[edit] Application

In general, substances that vaporize below ca. 300 °C (and therefore are stable up to that temperature) can be measured quantitatively. The samples are also required to be salt-free; they should not contain ions. Very minute amounts of a substance can be measured, but it is often required that the sample must be measured in comparison to a sample containing the pure, suspected substance.

Various temperature programs can be used to make the readings more meaningful; for example to differentiate between substances that behave similarly during the GC process.

Professionals working with GC analyze the content of a chemical product, for example in assuring the quality of products in the chemical industry; or measuring toxic substances in soil, air or water. GC is very accurate if used properly and can measure picomoles of a substance in a 1 ml liquid sample, or parts-per-billion concentrations in gaseous samples.

In practical courses at colleges, students sometimes get acquainted to the GC by studying the contents of Lavender oil or measuring the ethylene that is secreted by Nicotiana benthamiana plants after artificially injuring their leaves. These GC analyses hydrocarbons (C2-C40+). In a typical experiment, a packed column is used to separate the light gases, which are then detected with a TCD. The hydrocarbons are separated using a capillary column and detected with an FID. A complication with light gas analyses that include H2 is that He, which is the most common and most sensitive inert carrier (sensitivity is proportional to molecular mass) has an almost identical thermal conductivity to hydrogen (it is the difference in thermal conductivity between two separate filaments in a Wheatstone Bridge type arrangement that shows when a component has been eluted). For this reason, dual TCD instruments are used with a separate channel for hydrogen that uses nitrogen as a carrier are common. Argon is often used when analysing gas phase chemistry reactions such as F-T synthesis so that a single carrier gas can be used rather than 2 separate ones. The sensitivity is less but this is a tradeoff for simplicity in the gas supply.

[edit] GCs in popular culture

Movies, books and TV shows tend to misrepresent the capabilities of gas chromatography and the work done with these instruments.

In the U.S. TV show CSI, for example, GCs are used to rapidly identify unknown samples. "This is gasoline bought at a Chevron station in the past two weeks," the analyst will say fifteen minutes after receiving the sample.

In fact, a typical GC analysis takes much more time; sometimes a single sample must be run more than an hour according to the chosen program; and even more time is needed to "heat out" the column so it is free from the first sample and can be used for the next. Equally, several runs are needed to confirm the results of a study - a GC analysis of a single sample may simply yield a result per chance (see statistical significance).

Also, GC does not positively identify most samples; and not all substances in a sample will necessarily be detected. All a GC truly tells you is at which relative time a component eluted from the column and that the detector was sensitive to it. To make results meaningful, analysts need to know which components at which concentrations are to be expected; and even then a small amount of a substance can hide itself behind a substance having both a higher concentration and the same relative elution time. Last but not least it is often needed to check the results of the sample against a GC analysis of a reference sample containing only the suspected substance.

A GC-MS can remove much of this ambiguity, since the mass spectrometer will identify the component's molecular weight. But this still takes time and skill to do properly.

Similarly, most GC analyses are not push-button operations. You cannot simply drop a sample vial into an auto-sampler's tray, push a button and have a computer tell you everything you need to know about the sample. According to the substances one expects to find the operating program must be carefully chosen.

A push-button operation can exist for running similar samples repeatedly, such as in a chemical production environment or for comparing 20 samples from the same experiment to calculate the mean content of the same substance. However, for the kind of investigative work portrayed in books, movies and TV shows this is clearly not the case.

[edit] See also

[edit] References

  1. ^ a b c d Pavia, Donald L., Gary M. Lampman, George S. Kritz, Randall G. Engel (2006). Introduction to Organic Laboratory Techniques (4th Ed.). Thomson Brooks/Cole. pp. 797–817. ISBN 978-0-495-28069-9.

[edit] External links

http://www.themedicineprogram.com/home/article/Gas-liquid_chromatography

This may work for your urine drug screen, however there isn't much you can do mask a hair follicle drug test. The best solution for all you who found this post because you were looking for a way to pass your drug test is going to be... simply stop using drugs.

I'm not sure I understand what they are doing here, so far as I know you cannot detect alcohol in the hair even with a GCMS. Wonder if they can repeat these results and if they're accurate? More to come in the future.

Notice how the person collecting the hair sample on this video cuts the hair half an inch away from the persons head? The correct way to collect the hair sample for a hair drug test would be to cut the hair as close to the root as possible. Unless you don't care about the last month of drug abuse. Drugs grow into the hair follicle at an approximate rate of 1/2 inch per month.

Here is a training video posted by American Toxicology, on what they call the proper process for collecting a hair sample for a hair follicle drug test.

KTAR.com - `Crystal Darkness' Anti-Meth Campaign Coming to AZ

Meth. One word says it all. Now, a new documentary will take aim at the drug.

People throughout Arizona will have a chance to view the film, ``Crystal Darkness," on television from 6:30 p.m. to 7 p.m. on April 15. The first radio broadcast of the documentary will take place at the same time on News/Talk 92-3 KTAR.

The documentary explores the horrors of meth.

``The damage that's done, to young people in particular, is going to open a lot of eyes," former Suns' owner Jerry Colangelo said Monday. He is one of the promoters who brought the documentary, developed and first shown in Nevada, to Arizona.

Commander Chris Crockett of the Phoenix Police Department said meth is leading to more crime.

``One of the things you'll also find out when this program airs is how addictive it is," Crockett said, ``how one-time use can lead you down the path of addiction."

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The Crystal Darkness Campaign is a unique collaboration among the media, schools, law enforcement, recovery specialists and the business community. It was spearheaded by Secret Witness, a Nevada non-profit crime-stopping organization, and first aired in Nevada in January 2007.

Because of the publicity leading to the airing of Crystal Darkness, Secret Witness offered to assist other communities in hosting their own campaigns. Reno, Las Vegas, San Diego and communities across the state of Oregon have launched campaigns so far.

While the documentary airs in Arizona, dozens of professionally trained volunteers will stand by to receive and refer phone calls from families and victims seeking help with meth addiction. • Meth documentary



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The Meth Project is the largest advertiser in Montana, reaching 70-90% of teens three times a week. This is saturation-level advertising.

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Montana Meth Project Founder and Vice-chairman

The Entire Bibliography of Hair Drug Testing, as compiled by McBay. It keeps a record of everything that has any relationship to Hair Follicle Drug Testing between the years of 1980 - 2002! Click anywhere on the bibliography, to be directed to the official website.

HAIR DRUG TESTING BIBLIOGRAPHY

Compiled by Arthur McBay, Ph.D.
Updated 06/27/2002

Emeritus Professor, School of Pharmacy

University of North Carolina, Chapel Hill

Pre-1980

Goldblum R.W. et al. Barbiturate concentrations in the skin and hair of guinea pig, Invest Dermatol 1954;22:121-128.

Harrison W.H. et al. Incorporation of d-amphetamine into pigmented guinea pig hair. BrJ Dermatol 1974;91:415-418.

Maugh T.H. Hair: A diagnostic tool to complement blood, serum, and urine. Science 1978;202:1271-1273.

Baumgartner W.A. et al. Radio-immunoassay of hair for determining opiate abuse histories. J Nucl Med 1979;20:748.

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1980

Klug E. zur morphinbestimmung in kopfhaaren. Z Rechtsmed 1980;84:189-193.

Baumgartner W.A. et al. Detection of phencyclidine in hair J Forensic Sci 1981;26:576-581.

Smith F.P. et al. Detection of phenobarbital in bloodstains, semen, seminal stains, saliva, saliva stains, perspiration stains, and hair. J Forensic Sci. 1981;26:582-586.

Suzuki S. et al. Detection of trace amounts of methamphetamine in biological materials by mass fragmentometry. Koenshu-Iyo Masu Kenkyukai 1981;6:123-132.

Valente D. et al. Hair as the sample in assessing morphine and cocaine addiction. Clin Chem 1981;27:1952-53.

Baumgartner W.A. et al. Radioimmunoassay of cocaine in hair: Concise Communication. J Nucl Med 1982;26:790-792.

Nagai T. et al. Distribution of methamphetamine in the organs and tissue and its detection from hair. Teiko Igaku Zasshi 1982;5:213-220 (in Japanese)

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1983

Arnold W. Modern trends of chemical analysis in the drug scene in Topics in Forensic Analytical Toxicology. A. Maes ed. Elsevier Sci.Publ.,Amsterdam 1983.

Ishiyama I. et al. Detection of basic drugs, methamphetamine, antidepressants and nicotine, from human hair. J Forensic Sci 1983;28:380-385.

Niwagauchi T. et al. Determination of methamphetamine in hair after single and repeated administration to rats. Arch Toxicol 1983;52:157-164.

Puschel K. et al. Opiate levels in hair. Forensic Sci Int 1983;21:181-186.

Viala A. et al. Determination of chloroquine and monodesethylchloroquine in hair. J Forensic Sci. 1983;28:922-928.

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1984

Arnold W. et al. Haare als wichtage untersuchungen in der rechtsmedizin. Am univ Yaven Med 1984:22-24.

Nagai T. et al. Detection of codeine from animal hair and the lapse of time of its accumulation. Igaku to Seibutsugaku 1984;103:145-147. (in Japanese)

Suzuki 0. et al. Detection of methamphetamine and amphetamine in a single human hair by GC/CI. Koenchu-Iyo Masu Kenkyukai 1984;8:201-204.

Suzuki 0. et al. Analysis of methamphetamine in human hair by mass fragmentometry. Eisei Kagaku 1984;30:23-267.

Suzuki 0. et al. Detection of methamphetamine and amphetamine in a single human hair by GC/MS/CI. Forensic Sci 1984;29:611-617.

Suzuki 0. et al. Nails as useful materials for detection of methamphetamine and amphetamine abuse. Forensic Sci Int. 1984;24:9-16.

Takahashi K. Determination of methamphetamine and amphetamine in biological fluids and hair by GC. Nippon Hoigaku Zasshi 1984;38:313-336. (in Japanese)

Takahashi K. et al. Microanalysis of amphetamines III. Detection of amphetamines in the hair of monkeys treated with methamphetamine. Eisei Shikensho Hokoku 1984;102:21-24. (in Japanese).

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1985

Baumgartner W.A. et al. Detection of drug use by (RIA) of hair. Clin Nucl Med 1985;10(suppl):A3.

Haley N.J. et al. Analysis for nicotine and cotinine in hair to determine cigarette smoker status. Clin Chem 1985;31:1598-1600.

Manson P. et al. Hair analysis-A critical review. J Can Med Assoc.1985;133:186

Okamoto M. et al. Preparation and certification of human hair powder reference material. Clin Chem. 1985;31:1592-1597.

Sramek J.J. et al. Hair analysis for detection of phencyclidine in newly admitted psychiatric patients. Am J Psychiatry 1985;142:950-953.

Tagliaro F. Liquid chromatography with pre-column dansyl derivatisation and fluorimetric detection applied to the assay of morphine in biological samples. J Chromatog 1985;330:323-331.

Tagliaro F. et al. Quantitative determination of morphine in hair: a comparison between RIA and HPLC methods. Acta Med. Legalis et Soc. 1985;35:181-184.

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1986

Arnold W. RIA analysis of head hair for narcotics and substitutes. J Clin Chem Clin Biochem 1986;24:797

Marigo M. et al. Determination of morphine in the hair of heroin addicts by HPLC with fluorimetric detection. J Anal Toxicol 1986;10:158-161.

Parton D. et al. Quantitation of fetal cocaine exposure by RIA of hair. Ped.Res. 1986;21:372A

Sachs H. et al. GC/MS analysis of morphine and codeine in vitreous humor and hair. Beitr Gerichtl med 1986;44:281-286.

Smith F.P. Detection of cocaine metabolite in perspiration stain, menstrual bloodstain and hair. J Forensic Sci 1986;31:1269-1273.

Thanepohn S. A new wrinkle: Testing hair for drugs. US J Drug Alc Depend 1986;4:1-4

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1987

Arnold W. Radioimmunological hair analysis for narcotics and substitutes. J Clin Chem Clin Biochem 1987;25:753-757.

Arnold W. Analysis of organic drugs in from the head. Schriftenreihe des vereins fur Wasser-Boden-und Lufthygiene 1987:71;205-217.

Balabanova S. et al. Determination of cocaine in human hair by GC/MS. Z Rechtsmed 1987:98:235-240. ( RIA method pp. 229-234).

Centini F. et al. Determination of morphine in hair by immunochemical and GC/MS. Dev Anal Methods Pharm Biomed Forensic Science. Piemonte G. ed. Plenum Publ. NY NY 1987; pp 107-114.

Franchesin A. et al. Detection of morphine in hair with the Abbott TDX. Clin Chem 1987;11:2125

Hoyt D.H. et al. Drug testing in the workplace-are the methods legally defensible. JAMA 1987;284:504-509.

Kintz P et al. Identification by GCIMS of 6-monoacetylmorphine as an indicator of heroin abuse. Eur J Clin Pharmacol. 1987;37:531-532.

Marigo M. Determination of morphine and other opioids in the hair of heroin addicts by HPLC and MSIMS. Dev, Anal Methods Pharm Biomed Forensic Sci. Piemonte G. ed. Plenum Publ NY NY 1987.

Michalodimitrakis M. Detection of cocaine in rats from analysis of hair. Med Sci Law 1987;27:13-15.

Nagai T et al, A new analytical method for methamphetamine optical isomers and their determination in habitual users' hair by HPLC. Igaku to Seibutsugaku 1987;115:147-151.

Parton L. et al. Quantitation of fetal cocaine exposure by RIA of hair. Pediatr Res 1987;21:A372.

Pelli B. et al. Collisional spectroscopy for unequivocal and rapid determination of morphine at ppb level in the hair of heroin addicts, Biomed Environ Mass Spectroscopy 1987;14:63-68.

Tagliaro F. et al. Determination of morphine and other opioids in the hair of heroin addicts by RIA, HPLC, and Collision spectroscopy. Dev Anal Methods Pharm Biomed. Forensic Sci. Piemonte G. ed. Plenum Publ. NY NY 1987 pp 115-127

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1988

Balabanova S. et al. Detection of cocaine after repeated administration to sheep. Arch Toxicol Supp. 1988;12:398-401.

Balabanova S. et al. Determination of drugs in human hair by RIA Laboratoriummedizin 1988;12:332-334.

Baumgartner W.A. et al. Detection of drug use by analysis of hair. JNucl med (suppl) 1988;29;980.

Brunner H. et al. Determination of benzoylecgonine in human hair after cocaine abuse by GC/MS. Beitr Gerichtl med 1988;46:127-134.

Higuchi R. et al. DNA typing from single hairs. Nature 1988;332:543-546.

Martz R. The Identification of cocaine in hair by GC/MS and MSIMS. Crime Laboratory Digest 1988;15;68-73.

Nagai T. et al. Forensic toxicologic analysis of methamphetamine and amphetamine optical isomers by HPLC. Z Rechtmed. 1988;101:151-159.

Tagliaro F. et al. Detection of morphine in the hair of opium addicts with the Abbott TDX. Clin Chem 1988;34:1365-1366.

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1989

Bailey D.N. Drug screening in unconventional matrix: Hair analysis. JAMA 1989;262:3331.

Balabanova S. Determination of methadone in human hair by RIA. Z Rechtmed 1989;102:1-4.

Balabanova S. Determination of methadone in human hair by GC/MS. Z Rechtmed 1989:102:495-501.

Balabanova S. Methadone concentrations in human hair of the head, axillary and pubic hair. Z Rechtsmed 1989;102:293-296.

Balabanova S. et al. Tetrahydrocannabinol in the hair of hashish smokers. z Rechtsmed 1989;102:503-508.

Balabanova S. et al. Detection of cocaine morphine,phenobarbital, and methadone in head,axillary,and pubic hair. Laboratoriums medizin 1989;13:46-47.

Baumgartner W.A. et al. Hair analysis for drugs of abuse. J Forensic Sci 1989;34:1433-1453.

Baumgartner W.A. et al. Hair analysis for drugs of abuse. Clin Chem 1989;10:7-21.

Gropper B.A. Drug detection through hair analysis. Law Enforcement Tech. 1989 p.18.

Graham K. et al. Determination of gestational cocaine exposure by hair analysis. JAMA 1989;262:3328-3330.

Harkey M.R. et al. Hair analysis for drugs of abuse in Advances in Analytical Toxicology, Vol.II, Baselt RC ed. Yearbook Medical Pub. Chicago 1989, pp.298-329.

Midkiff C.R. Detecting drugs in hair: Targets and techniques. Scientific Sleuthing Rev. 1989;13:14-15.

Nakahara Y. et al. Enzyme linked immunosorbent assay (ELISA) using monoclonal antibody to detect methamphetamine in urine and hair. Eisei Kagaku 1989;35:333-338.

Offidani C. et al. Drugs in hair, a new extraction procedure. Forensic Sci Int 1989;41:35-39.

Sachs H. et al. Results of comparative determination of morphine in human hair using RIA and GC/MS. JClin Chem Clin Biochem 1989;27:873-877.

Sato R. et al. Human scalp hair as evidence of individual dosage history of haloperidol: Prospective study. Ther Drug Monit 1989;11:686-691.

Suzuki S. et al. Analysis of methamphetamine in hair,nail,sweat, and saliva by mass fragmentometry. JAnal Toxicol. 1989;13:175-178.

UematSu T. et al. Human scalp hair as evidence of individual dosage history of haloperidol: Method and retrospective study. Eur J Clin Pharmacol 1989;37:239-244.

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1990

Anstadt G.W. Hair analysis in drug screening. JOccup Med 1990;32:666-669. Arnold W. The determination of drugs and their substitutes in human hairs. Forensic Sci Int 1990;46:i7-i8.

Balabanova S. et al. Detection of caffeine in human hair by EIA and GC/MS Scientific Symposium Rechtsmedizin und Forensiche Toxikologie, Hamburg, Oct.2/3,1990, pp.118-126.

Balabanova S. The importance of hair throughout history and in modern toxicology. Laboratoriummedizin 1990;14:29-35.

Balabanova S. et al. Detection of nicotine in hair. Deut Apoth Zeit 1990;130:2200-2201.

Baumgartner W.A. Discussion of Hair analysis for drugs of abuse J Forensic Sci. 1990;35:778-779.

Baselt R.C. et al. On the dermal absorption of Cocaine. J Anal Toxicol 1990;14:383-384.

Brewer C. Hair analysis for drugs of abuse (letter). Lancet 1990;335:980.

Bogusz M. Comment on, Tetrahydrocannabinol in the hair of hashish smokers and on Dr. Balabanova’s Answer to the observations of Kaferstein and Sticht. Z Rechtmed 1990;103:621-622.

Cone E.J. Testing human hair for drugs of abuse: i. Individual dose and time profiles of morphine and codeine in plasma, saliva, urine and beard compared to drug-induced effects on pupils and behavior. J Anal Toxicol 1990;14:1-7.

Kaferstein H. et al. Comment on detection of methadone in human hair by GC/MS and Tetrahydrocannabinol in the hair of hashish smokers. Z Rechtmed 1990;103:393-396.

Martinez F. et al. Hair analysis. Science, (letter) 1990;250:1070.

Matsuno H. et al. The measurement of haloperidol and reduced haloperidol in hair as an index of dosage history. Br J Clin Pharmacol 1990;29:187-194.

Maurer H.H. et al. Toxicological detection of Pholcodine and its metabolites in urine and hair using RIA, FPIA, EIA, and GC/MS. Int J Legal Med (Formerly, z Rechtsmed) 1990;104:43-46.

Nakahara Y et al. Hair analysis for drugs of abuse: II. Hair analysis for monitoring methamphetamine abuse by isotope dilution GC/MS. J Forensic Sci i990;46:243-254.

Nakahara Y. Drug analysis in hair. For monitoring methamphetamine abuse history. Byoin Yakugaku 1990;16:233-247.(in Japanese).

Newman J. Hair analysis is proving effective in determining drug use. American Health 1990;9:20

Sauls F.P. Discussion of "Hair analysis for drugs of abuse" (letter) J Forensic Sci 1990;35:778.

Scheller M. et al. Demonstration of codeine abuse by hair analysis. Deut Med Wochenschr 1990;115:1313-1315.

Strang J. et al. Hair analysis for drugs of abuse. Lancet 24 Mar i990, p. 740.

Tsunoda N. Forensic science and analysis of hair and toxicants. Bunseki 1990;10:816-817. (in Japanese)

Uematsu T. et al. Human scalp hair as evidence of individual dosage history of haloperidol: Longer-term follow-up study. Ther Drug Monit 1990;12:582-583.

Uematsu T. et al. Human scalp hair as evidence of individual dosage history of haloperidol: A possible linkage of haloperidol excretion into hair with hair pigment. Arch Dermatol Res 1990;282;120-125.

Welch R.A. et al. Radioimmunoassay of hair: A valid technique for determining maternal cocaine abuse. Substance Abuse 1990;11:214-217.

Wish E. et Al. Drug testing by the criminal justice systems: Methods, research, and applications, Crime and Justice,Vol.3, Drugs and Crime 1990,Univ. Chicago, pp. 321-390.

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1991

Baer J.D. et al. Hair analysis for the detection of drug use in pretrial, probation, and parole populations. Federal Probation 1991;LV:3-10.

Baumgartner W.A. Discussion of "Hair analysis for drugs of abuse" J Forensic Sci. 1991;36:629-630.

Cartmell LW et al. Cocaine metabolites in pre-Columbian mummy hair. J OK State Med Assoc. 1991;84:11-12.

Cone E.J. et al Testing human hair for drugs of abuse. II. Identification of unique cocaine metabolites in hair of drug abusers and evaluation of decontamination procedures. J Anal Tox 1991; 15:250-255.

Denk R. et al. Quality assurance in examination of hair for drugs of abuse. Toxichem & Krimtech. 1991;58:79-83.

Goldberger B.A. et al. Testing human hair for drugs of abuse. III. Identification of heroin and 6-acetylmorphine as indicators of heroin use. J Anal Tox 1991;15:226-231.

Harkey M. et al. Simultaneous quantitation of cocaine and its major metabolites in human hair by CC/CI/MS. J Anal Toxicol 1991;15:260-265.

Martz R. et al. The use of hair analysis to document a cocaine overdose following a sustained survival period before death. J Anal Toxicol 1991;15:279-281.

Magura S. et al. The validity of hair analysis for detecting cocaine and heroin use among addicts. Int J Addict 1991;27:54-69.

Maurer H.H. et al. Forensic-toxicolgic detection of pholcodine in urine and hair. Beitr Gerichtl med l991;48:37-39.

McBay, A.J. Hair Drug Testing. Proc 29th Int meeting of TIAFT Kaempe B. ed. Copenhagen 1991:29-41.

Mieczkowski T. et al. Concordance of three measures of cocaine use in an arrestee population: Hair, urine. and self-report. J Psychoactive Drugs 1991;23:241-249.

Miyazawa N. et al. Ofloxacin in human hair determined by HPLC. Forensic Sci Int 1991;51:65-77.

Nakahara Y. et al. Hair analysis for drug abuse: l. Determination of methamphetamine and amphetamine in hair by stable isotope dilution GC/MS method. J Forensic Sci 1991;36:70-78.

Needleman S.B. Discussion of hair analysis for drugs of abuse. J Forensic Sci. 1991;36:628

Ostrea E.M. Jr. et al. Detection of prenatal drug exposure in the pregnant women and her newborn infant. Clinics in Perinatol 1991;18:620-645.

Pelligrino S. et al. Optimization of the acid extraction of morphine from hair. G Ital Chim Clin 1991;16:409-413.

Reuschel S.A. et al. Benzoylecgonine detection in hair samples of jail detainees using RIA and GC/MS. J Forensic Sci 1991;36:1179-1185.

Rob S. Drug detection by hair analysis. Army Lawyer Jan 1991: 10-16.

Uematsu T. et al. The measurement of haloperidol and reduced haloperidol in neonatal hair as an index of placental transfer of maternal haloperidol. Ther Drug Monit 1991;13:183-187.

Uematsu T et al. The measurement of ofloxacin in hair as an index of exposure. Eur J Clin Pharmacol 1991: 40: 581-584.

Uematsu T. et al. The measurement of haloperidol and reduced haloperidol in neonatal hair as an index of placental transfer of maternal haloperidol. Ther Drug Monit. 1991;13:1991

Yamada H. et al. Analysis of cocaine in hair by GC/MS. Hochudoku 1991;9:106-107.

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1992

Ahrens B. et al. Detection of morphine and monoacetylmorphine in human hair. Fresenius J Anal Chem. 1992;344:559-560.

Balabanova S. et al. First identification of drugs in Egyptian mummies. Naturwissenschaften 1992;79:358.

Baumgartner W.A et al Hair analysis for drugs of abuse: Decontamination issues, in Recent Dev Ther Drug monitor and Clin Toxicology, Sunshine I, ed. 1992, pp.577-597, Marcel Dekker, Inc. NY NY.

Callahan C.M. et al. Measurement of gestational exposure: Sensitivity of infants, hair, meconium, and urine. J Pediatr 1992;120:763-768.

Curcurato 0. et al. Ion-trap spectrometry applications in forensic sciences. I. Identification of morphine and cocaine in hair extracts of drug addicts. Rapid Commun mass Spectrom 1992;6:434-437.

Ferko A.P. et al. The accumulation and disappearance of cocaine and benzoylecgonine in rat hair following prolonged administration of cocaine. Life Sci 1992;51:1823-32.

Forman R. et al. Accumulation of cocaine in maternal and fetal hair; The dose response curve. Life Sci 1992;50:1333-1341.

Fritch D. et al. Cocaine and some of its products in hair by RIA and GC/MS. J Anal Toxicol 1992;16:112-114.

Henderson G.L .et al. Cocaine and metabolite concentrations in the hair of South American coca chewers. J Anal Toxicol. 1992;16:199-201.

Janzen K. Concerning norcocaine, ethylbenzoylecgonine, and the identification of cocaine use in human hair. (Letter), J Anal Toxicol 1992;16:402.

Kidwell D.A. et al. Hair analysis: Techniques and potential problems. Recent Dev Ther Monitor and Clin Toxicol. Sunshine I, ed. Marcel Dekker NY NY 1992:555-563.

Kintz P. et al, Evaluation of nicotine and cotinine in human hair. J Forensic Sci 1992;37 :72-76.

Kintz P. et al. Detection of drugs in human hair using Abbott ADx with confirmation by GC/MS. J. Forensic Sci 1992;37:328-331.

Kintz P. et al. Hair analysis for detection of beta-blockers in hypertensive patients. Eur J Clin Pharmacol 1992;42:351-352.

Kintz P. Gas chromatographic analysis of nicotine and cotinine in hair. J Chromatogr 1992;580:347-353.

Kintz P. et al. Tobacco, pharmaceutics and drugs of abuse during pregnancy. Determination of gestational exposure by hair analysis. (Fr) La Presse med 1992;44;19-26.

Kintz P. et al. Detection of drugs in human hair for clinical and forensic applications. Int J Legal Med 1992;105:1-4.

Kintz P. et al. Toxicological investigations on unusual materials (hair and vitreous humor): Interest and limitations. Arch Toxicol Supp. 1992;15 (Med Toxicol 282-285.)

Klein J. et al. Fetal distribution of cocaine: case analysis. Pediat. Pathol. 1992;12:463

Koren G. et al. Hair analysis of cocaine: Differentiation between systemic exposure and external contamination. J Clin Pharmacol 1992;32:671-675.

Koren G. et al. Hair tests to verify gestational cocaine exposure. Rec. Dev. Ther Drug Monitor. Clin. Toxicol.Sunshine I.ed Dekker NYNY. 1992;569-573.

Koren G. et al. Biological markers of intrauterine exposure to cocaine and cigarette smoking. Dev. Pharmacol Ther. 1992;18:228-236.

Magura S. et al. The validity of hair analysis for detecting cocaine and heroin use among addicts. Int J Addict 1992;27:51-59.

Marsh A. et al. An investigation of the effect of washing upon the morphine content of hair measured by a radioimmunoassay technique. J Pharm Biomed Anal. 1992;10:89-93.

Mieczkowski T. New approaches in drug testing: A review of hair analysis. Ann Am Acad Pol & Soc Sci. 1992;521:132-150.

Miyazawa N. et al. Analysis of ofloxacin in hair as a measure of hair growth and time marker for hair analysis. Ther Drug Monit. 1992;29:525-528.

Moeller M.R. et al. Identification and quantitation of cocaine and its metabolites, benzoylecgonine, and ecgonine methyl ester,in hair of Bolivian coca chewers by GC/MS. J Anal Tox 1992;16:291-296.

Moeller M.R. Drug detection in hair by chromatographic procedures (Review) Chromatogr 1992;580:125-134.

Moriya F. et al. Presumption of a history of methamphetamine abuse by postmortem analysis of hair and nails. Arukoru Kenkyu to Yakubutsu Tzon 1992;27:152-i58.

Nakahara Y. et al. Hair analysis of drugs of abuse, III. Movement and stability of methoxyamphetamine along hair shaft with hair growth. J Anal Toxicol 1992;16:253-257.

Nakahara Y. et al. Hair analysis for drugs of abuse. IV. Determination of total morphine and confirmation of 6-acetylmorphine in monkey and human hair by GCIMS. Arch Toxicol 1992;66:669-674.

Nakahara Y. et al. Hair analysis for drugs of abuse V. The facility of the incorporation of cocaine into hair over its major metabolites, benzoylecgonine, and ecgonine methyl ester. Arch Toxicol 1992;66:449-449.

Nakahara Y. et al. GC/MS analysis of drugs and metabolites in hair for diagnosis of chronic drug abuse. on cocaine,heroin,and amphetamines. Nippon Iyo Masu Supek utoru Gakkai Koenshu. 1992;17:207-209. (in Japanese)

Pirozhkov S. V. et al. Gas chromatographic detection of cocaine and cocaethylene of mice chronically injected with cocaine or cocaethylene and fed ethanol. Forensic Sci Int. 1992;57:99-107.

Poet T.A. et al. Effect of murine retroviral infection on hair and serum levels of cocaine and morphine. Forensic sci Int 1992;54:29-38.

Runne U. et al. Sequential concentration of chloroquine in human hair correlates with ingested dose and duration of therapy. Acta Dermato-Venereolog 1992;72:355-357.

Smith F.P. Forensic hair analysis: Cocaine. Rec Dev Ther Drug Monitor. Clin Toxicol. Sunshine I ed. Marcel Dekker NY NY 1992, 565-568.

Sramek J.J. et al. Detection of benzodiazepines in human hair by radioimmunoassay. Ann Pharmacother 1992;26:469-471.

Tracqui A. et al. Determination of amitriptyline in the hair of psychiatric patients. Human and Experimental Toxicology 1992;11:363-367.

Uematsu T. Possible effect of pigment on the pharmacokinetics of ofloxacin and its excretion in hair. J Pharmaceut Sci. 1992;81:45-48.

Uematsu T. et al. Steady-state pharmacokinetics of haloperidol and reduced haloperidol in schizophrenic patients: Analysis of factors determining their concentrations in hair. J Pharmaceut Sci. 1992;81:1008-1011.

Uematsu T. Establishment of a method to analyse drugs in hair and its application for determining patient compliance (Japanese). Nippon Yakurigaku zasshi Folia Pharmacologica Japonica 1992;100:475-483.

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1993

Baumgartner W.A. et al. Comments on the paper by Blank and Kidwell: External contamination of hair by cocaine:an issue in forensic interpretation. Forensic Sci Int 1993;63:157-160.

Baumgartner W.A. et al. Sample preparation techniques. Forensic Science Int.1993;63:121-i35.

Blank D.L. et al. Comments on the paper by W.A. Baumgartner and VA Hill: sample preparation techniques. Forensic Science Int 1993;63:137-143.

Blank D.L. et al.. External contamination of hair by cocaine. An issue in forensic interpretation. Forensic Science Int. 1993;63:145-i56.

Bost R.O. Hair analysis-perspectives and limitations. Forensic Science Int.1993;63:31-42.

Brewer C. Hair analysis as a tool for monitoring and managing patients on methadone maintenance. Forensic Science Int. 1993;63:277-283.

Brewer C. Treatment of cocaine abuse with monoamine oxidase inhibiters. Br J Psychiatry 1993;163:815-816.

Brewer C. Hair analysis for monitoring drug use (Letter). Addiction 1993;88:1291-1292

Cassani M. et al. Analytical requirements, perspectives and limitations of immunological methods for drugs in hair. Forensic Science Int. 1993;63:175-184.

Chiarotti M. Overview on extraction procedures. Forensic Science Int. 1993;63:161-170.

Cone E.J. et al. The occurrence of cocaine, heroin and metabolites in hair of drug abusers. Forensic Science Int. 1993;63:55-68.

Drug use measurement: Strengths, limitations, and recommendations for improvement. 1993 GAO/PEND-93-18 Washington DC. pp. 58-60,68-69,72.

DiGregorio G.J. et al. Prevalence of cocaethylene in the hair of pregnant women. (Letter) J Anal Toxicol 1993;17:445-446.

Ferrara S.D. Importance of quality assurance in testing drugs of abuse (letter). Forensic Science Int. 1993;63:305-309.

Gamelea N.B. Antibodies to drugs as indicators of chronic drug use. An alternative to toxicological hair analysis. Forensic Science Int. 1993;63:285-293.

Gamelea N.B et al. Immune response to opiates. New findings in heroin addicts investigated by means of an original enzyme immunoassay and morphine determination in hair. Life Sci 1993;53:99-105.

Harkey M.R. Anatomy and physiology of hair. Forensic Science Int. 1993;63:9-18. Henderson GL. Mechanisms of drug incorporation into hair. Forensic Science Int. 1993;63:19-29.

Kalasinsky K.S. et al. Hair analysis by infrared microscopy for drugs of abuse. Forensic Science Int. 1993;63:253-260.

Kidwell D.A. et al. Comments on the paper by Baumgartner and Hill: Sample preparation techniques. Forensic Sci Int. 1993;63:137-143.

Kidwell D.A. Analysis of phencyclidine and cocaine in human hair by tandem mass spectrometry. J Forensic Sci 1993;38:272-284.

Kikura R. Discrimination between methamphetamine use and deprenyl use by hair analysis. Hochudoku 1993;11:100-101.

Kintz P. et al. Evidence of gestational heroin or nicotine exposure by analysis of fetal hair. Forensic Science Int. 1993;63:99-104.

Kintz P. et al. Nicotine analysis in neonates hair for measuring gestational exposure to tobacco. J Forensic Sci 1993;38:119-123.

Kintz P., et al. Opiate concentrations in human head, axillary, and pubic hair J Forensic Sci 1993,38:657-662.

Kintz P. et al. Determination of meprobamate in human plasma, urine, and hair by gas chromatography and electron impact mass spectrometry. J Anal Toxicol 1993;17:408-410.

Kintz P. Determination of buprenorphine and its dealkylated metabolite in human hair. (Letter) J Anal Toxicol. 1993;17:443-444.

Kintz P. et al. Determination of gestational opiate, nicotine, benzodiazepine, cocaine, and amphetamine exposure by hair analysis. J Forensic Sci Soc. 1993;33:139-142.

Kintz P. et al. Pharmacological studies of meprobamate in human beard hair. Int J Legal Med. 1993;105:283-287.

Klein J. et al. Hair analysis as a marker for fetal exposure to maternal smokng. N Engl J Med 1993;328: 66-67.

Mangin P. et al. Variability of opiates concentration in human hair according to their anatomical origin: Head, axillary, and pubic regions. Forensic Science Int 1993;63:77-83.

Marsh A. Challenging declarations of abstinence by the interpretation of morphine in hair by radioimmunoassay J Pharm Biomed Anal 1993;11:693-698.

Marques P.R. et al. Cocaine in the hair of mother-infant pairs: Quantitative analysis and correlations with urine measures and self-report. Am J Drug Alcohol Abuse 1993;19:159-175.

Martinez F. et al. Cocaine metabolite in hair and urine of drug users. J Anal Toxicol 1993;17:138-142.

McIntosh N.D. First Identification of drugs in Egyptian mummies(letter) Naturwissenschaften 1993;80:245-246.

Mieczkowski T. Testing hair for illicit drug use. Natl Inst Justice 1993 January.

Mieczkowski T. et al. An evaluation of patterns of racial bias in hair assays for cocaine. Black and white arrestees compared. Forensic Science Int 1993;63:85-98.

Mizuno A. et al. Analysis of nicotine content of hair for assessing individual cigarette-smoking behavior. Ther Drug Monit 1993;15:99-104.

Moeller M.R. et al. Hair analysis as evidence in forensic cases. Forensic Science Int. 1993;63:43-53.

Moeller M.R. et al. Simultaneous determination of drugs of abuse (opiates, cocaine, and amphetamine) in human hair by GC/MS and its application to a methadone treatment program. Forensic Science Int 1993;63:185-206.

Nakahara Y. What kind of information can be found by hair analysis? The limitations of urinalysis and advantages of hair. Hochudoku 1993;11:90-93.

Nakahara Y. et al. Hair analysis for drugs of abuse. VI. The excretion of methoxyamphetamine and methamphetamine into beards of human subjects. Incorporation and movement of drugs in hair. Forensic Science Int 1993;63:109-119.

Offidani C. et al. Drug distribution in the head, axillary, and pubic hair of chronic addicts. Forensic Science Int 1993;63:105-108.

Offidani C. et al. Improved enzymatic hydrolysis of hair. Forensic science Int. 1993;63:171-174.

Polletini A. et al. Rapid and highly selective GC/MS detection of heroin and its metabolites in hair. Forensic Science Int. 1993;63:217-225.

Sachs H. et al. Comparison of quantitative results of drugs in human hair by GC/MS. Forensic Science Int. 1993;63:207-216.

Sachs H. Dihydrocodeinone in hair. Int J Legal Med 1993;105:247-250.

Sato I. Chlorpromazine in human scalp hair as an index of dosage history: Comparison with simultaneously measured haloperidol. Eur J Clin Pharmacol 1993;44:439-444.

Schutz H. et al. The detection of drugs and other foreign substances in hair. Pharm Unserer Zeit. 1993;22:65-78.

Springfield A.D. et al. Cocaine and metabolites in the hair of ancient Peruvian coca leaf chewers. Forensic Science Int 1993;63:269-275.

Stark M.M. Further ethical issues raised by hair analysis for drugs. Addiction 1993;88:1292.

Staub C. Hair analysis: Its importance for the diagnosis of poisoning associated with opiate addiction. Forensic Science Int 1993;63:69-75.

Strang J. et al. Hair analysis for drugs: Technological breakthrough or ethical quagmire. Addiction 1993;88:163-166.

Comments on Strang’s paper in Addiction 1994;89 by: Evans D. 295-6, Almond B. 296-7, Howard G. 299, Erin C. 299-300 Sunshine I. Mandatory drug testing in the United States. Forensic Science Int. 1993;63:1-7.

Tagliaro F. Capillary electrophoresis for the investigation of illicit drugs in hair determination of cocaine and morphine.J Chromatogr 1993;638:303-309.

Tagliaro F. et al. High sensitivity low-cost methods for determination of cocaine in hair: HPLC and capillary electrophoresis. Forensic Sci Int 1993;63:227-238.

Traldi P. et al. Ion trap mass spectrometry, a new tool in the investigation of drugs of abuse in hair. Forensic Science Int. 1993;63:239-252.

Uematsu T. Therapeutic drug monitoring in hair samples: Principles and practice. Clin Pharamcokinetics 1993;25:83-87.

Uematsu T. The measurement of a new antimicrobial quinolone in hair as an index of drug exposure. Br J Clin Pharmacol 1993;35:199-203.

Uematsu T. A new antimicrobial (quinolone) analysed in hair as an index of drug exposure and as a time marker. J Pharm Pharmacol 1993;45:1012-1014.

Uematsu T. 1-(Tetrahydro-2-furanyl)-5-fluorouracil (Ftorafur) determined in rat hair as an index of drug exposure. J Pharmaceut Sci. 1993;82:1272-i274.

Uematsu T. Utilization of hair analysis for therapeutic drug monitoring with a special reference to ofloxacin and to nicotine. Forensic Science Int. 1993;63:261-268.

Wang W.L. et al. Immunoassay evidence for fentenyl in hair of surgery patients. Forensic Sci Int 1993;61:65-72.

Welch M. et al. Interlaboratory comparison studies on the analysis of hair for drugs of abuse. Forensic Science Int. 1993;63:295-303.

Welch M. et al. Hair analysis for drugs of abuse: Evaluation of analytical methods, Environmental issues and development of reference materials. J Anal Toxicol 1993;17:389-398.

Back to Index

1994

Almond B. Hair analysis for drugs: defining the ethical questions. Addiction 1994;89:296-297

Arnold W. et al. Hair analysis for medicaments-The best proof for a drug career. Fresenius J Anal Chem. 1994;348:484-489.

Baumgartner W.A.. Ligand assays of enzymatic hair digests. US Patent no. 5,324,042 June 24, 1994.

Edders P. et al. Subcritical fluid extraction of opiates in hair of drug addicts. J Chromatogr B 1994;658:75-86

Eliopoulos C. Hair concentrations of nicotine and cotinine in women and their newborn infants. JAMA 1994;271:621-623.

Erin CA. Some comments on the ethics of hair analysis for drugs. Addiction 1994; 89:298-300

Evans D. Hair analysis for drugs: Where is the ethical quagmire? Addiction 1994;89:295-296.

Feucht T. et al. Drug use among juvenile arrestees: A comparison of self-report, urinalysis,and hair assay. J Drug Issues 1994;24:99-116.

Forman R. et al. Prevalence of fetal exposure to cocaine in Toronto, i990-i991. Clin Inv Med 1994;17:206-211.

Goldberger B.A. Disposition of heroin and its metabolites in heroin-related deaths. J Anal Toxicol 1994;18:22-28.

Grant T. Cocaine exposure during pregnancy: Improving assessment with RIA of hair. Obstet Gynecol 1994;85;524-531.

Hindin, R. et al. RIA of hair for determination of cocaine, heroin, and marijuana exposure: comparison with self-report. Int J Addict. 1994;29:771-789.

Howard J. Hair analysis for drug testing - where is it leading? Addiction 1994;89:297-299.

Klein J. et al. A method for the simultaneous measurement of cocaine and nicotine in neonate hair. Ther Drug Monit. 1994;16:67-70.

Kintz P. et al. Ethylmorphine concentrations in human samples in an overdose case. Arch Toxicol 1994;68:210-2ii.

Kintz P. et al. Hair analysis for buprenorphine and dealkylated metabolic by RIA and confirmation by LC/ECD. J Forensic Sci. 1994;39:1497-1503.

Kintz P. Hair extraction for drugs of abuse by Coca Cola ; The ultimate method. Acta Medicin Legalis 1994; 44: 177-179.

Klein J. et al. A method for simultaneous measurement of cocaine and nicotine in neonatal hair. Therapeut Drug Monit. 1994;16:67-70.

Marsh A et al. RIA of drugs of abuse in hair. 1. methadone in human hair, method adaptation and the evaluation of decontamination procedures. J Pharmaceut & Biomed Appl. 1994;12:1123-1130.

Mizuno A. et al. Simultaneous determination of ofloxacin, norfloxacin and ciprofloxacin in human hair by HPLC and fluorescence detection. J Chromatogr B. 1994;653:187-193.

Nakahara Y. et al. Hair analysis for drugs of abuse VII. The incorporation rates of cocaine, benzoylecgonine and ecgonine methyl ester into rat hair and hydrolysis of cocaine in rat hair. Arch Toxicol. 1994;68:S4-S9.

Nakahara Y. et al. Hair analysis for drugs of abuse VIII. Effective extraction and determination of 6-acetylmorphine and morphine in hair with trifluoracetic acid and methanol for the confirmation of retrospective heroin use by GCIMS. J Chromatogr B:Biomedical Appl. 1994:657:93-101.

Nilsen T. et al. Uptake of nicotine in hair during controlled environmental air exposure: Evidence for a major contribution of environmental nicotine to the overall nicotine found in hair from smokers and non-smokers. Pharmacol ToxiCol. 1994;75:136-i42.

Potter S. et al. Maternal cocaine use without evidence of fetal exposure. J Pediatr. 1994;125:652-654

Reid R.W. et al. The in vitro differential binding of benzoylecgonine to pigmented human hair samples. J Toxicol Clinical Toxicol. 1994;32:404410.

Smith F.P. A discussion of opiate concentrations in human hair. (Letter) J Forensic Sci 1994;39:301-302. Authors' Response (Letter) Ibid 302-303.

Tagliaro F. et al. Reversed-phase HPLC of cocaine in plasma and human hair with direct fluorimetric detection. J Chromatogr B i994;674:207-215.

Uematsu T. The measurement of temafloxacin in human scalp hair as an index of drug exposure. J Pharmaceut Sci. 1994;83:42-45

Wang W.L. et al. Simultaneous assay of cocaine, heroin, and metabolites in hair, plasma, saliva, and urine by GC/MS. J Chromatogr. B. 1994;660:279-290.

Zahlsen K. et al. Nicotine in hair of smokers and non-smokers: Sampling procedure and GC/MS analysis. Pharmacol ToxiCol. 1994;75:143-149.

Back to Index

1995

The following papers are from: Proc Intl Conf & Wkshp for Hair Analysis in Forensic Toxicology. deZeeuw RA et al eds, Abu Dhabi UAE 1995.

Baumgartner W. et al. Review of selected field studies on hair analysis in the criminal justice system. pp. 413-430

Cairns T. et al. Determination of carboxy-THC in hair by mass spectrometry/ mass spectrometry. pp. 185-193.

Cirimele V. et al . Supercritical fluid extraction of human hair for opiates. pp. 499

Cone E.J. et al. Hair as a tool in forensic toxicology. pp.50-59.

Cone E.J.. et al. Testing for cocaine in hair. pp. 136.-160.

deZeeuw R.A. et al. Hair analysis by ion mobility spectrometry. pp. 334-350.

Drummer O. et al. Detection of anti-depressant drugs in hair.. pp. 217-224.

Drummer O. et al. Extraction of psychotropic drugs in hair. pp. 326-333.

Ferrara S.D. et al. Endogenous substances in hair. pp. 225-260.

Franzelius C. et al. Monitoring of phenobarbital in hair: A suitable method for the detection of non-compliance. p. 500

Huestis M.A. et al. To accept or not accept, that is the question: Hair testing results in the American courts. pp. 467-481.

Jurado C. et al. Interlaboratory studies in Spain and France. pp. 385-397.

Kintz P. et al. Testing human hair for cannabis. Identification of natural ingredients of cannabis sativa and metabolites of THC. pp. 194-202.

Kippenburger D.J. et al. A wash kinetic-digestion method of hair analysis for distinguishing between drug -use and contamination. pp. 299-325.

Klein J. et al. Clinical utilization of the neonatal hair test for cocaine: A four year experience in Toronto. pp. 431-442.

Mangin P. Hair analyses and their acceptance in court (Southern France) PP. 482-487.

Mieczkowski, T. et al. An Evaluation of Patterns of Race and Sex Bias in Cocaine Assays of Human Hair, pp. 90-106.

Miller M. et al. The analysis of hair by electrospray ionization HPLC/MS. pp.282-298.

Moeller M. et al. The use of hair drug testing in criminal investigations. pp. 398-412.

Moeller M.R. et al. Narcotics. pp. 107-117.

Montagna M. et al. Human hair certified reference materials for drugs of abuse analysis: Development of a program for the preparation of CRMs for opiates. pp. 370-384.

Nakahara Y. et al. Effect of structural factors on incorporation of drugs into hair: The incorporation rates of amphetamine analogs. pp. 28-49

Nakahara Y. et al. Findings in hair analysis for some hallucinogens (LSD, MDA/MDMA and PCP. pp. 161-184.

Potsch L. On the physiology and ultrastructure of human hair. pp. 1-27

Rollins D. et al. Models for studying the distribution of drugs of abuse into hair. 60-75.

Rollins D. et al. Distribution of codeine into hair. pp. 118-135.

Sachs H. Hair analyses and their acceptance in courts (Germany). pp. 488-493.

Segura J. Possibilities of ElLISA methodologies for hair analysis. pp. 351-369.

Spiehler V. Immunological methods for drugs in hair. pp. 261-281.

Staub C. et al. Analysis of drugs in hair by an automated solid phase extraction method (SPE). p. 497.

Strano-Rossi S. et al. Study on the intrauterine exposure to cocaine through the analysis of hair from pathological newborns. p. 501.

Tabernero M.J. et al. Mandatory hair analysis in Spain and correlation with urine measure and self-report. p. 496.

Uematsu T. et al. Using of time marker in hair to improve the reliability for sectional analysis versus time of exposure. pp. 76-106.

Uematsu T. et al. Axial distribution of nicotine content along hair shaft as an indicator of individual smoking behavior . pp. 203-216.

Williams J. Sectional hair analysis as a potential index of therapeutic compliance in an epileptic population. pp. 443-466.

Other 1995 Articles

Ahrens B, et al. Detection of cloazepine in hair one year after burial. Arch Kriminol 1995;196:138.

Baumgartner W.A., et al. Forensic drug testing by mass spectrometric analysis of hair. Forensic Application of mass Spectrometry ed. I. Yinon, CRC Press, Boca Raton, 1995, pp. 61-94.

Baumgartner W.A.. Hair analysis method. US Patent no. 5,466,579, Nov. 14,1995.

Bermejo-Barrera A. et al. Hair and urine analysis: relative distribution of drugs and their metabolites. Forensic Sci Int. 1995;70:200-210.

Blank D.L. et al. Decontamination procedures for drugs of abuse: are they sufficient?. Forensic Sci Int. 1995;70:13-38.

Cirimele V. et al. Determination of gestational codeine exposure by analysis of fetal hair. Intl Assoc Forensic Toxicol. 1995;25:20-22.

Cirimele V.et al. Testing human hair for cannabis. Forensic Sci Int. 1995;70:175-182.

Cirimele V. et al. Testing a drug addict's hair for pholocodine. Case Notes: Tox Talk 1995; 19: 6

Cirimele V. et al. Drug concentrations in human hair after bleaching. (Letter) J Anal Toxicol. 1995;19:331-332.

Cirimele V. et al. Supercritical fluid extraction of drugs in drug addict hair. J Chromatagr B Biomedical Applications 1995; 673: 173-181.

Cook R.F. et al. Methods for assessing drug use prevalence in the workplace: A comparison of self-report, urinalysis, and hair analysis Intl J Addictions 1995;30:403-426.

Couper F.J. et al. Extraction of psychotropic drugs from human scalp hair. J Forensic Sci 1995;40:83-86.

Couper F.T. et al. Detection of antidepressant and antipsychotic drugs in postmortem human scalp hair. J Forensic Sci. 1995;40:87-90.

DuPont R.L. Drug testing by urine and hair analysis: complementary features and scientific issues. Forensic Sci Int 1995;70:63-76.

Gygi S.P. et al. Distribution of codeine and morphine into rat hair after long-term daily dosing with codeine. J Anal Toxicol 1995;19:387-391.

Gerstenberg B. et al. Nicotine and cotinine accumulation in pigmented and unpigmented rat hair. Drug Metab Dispos 1995;23:143.

Coullel J.P. et al Phenobarbital in hair drug monitoring. Forensic Sci Int 1995;70:191-202.

Jurado C. et al Simultaneous quantification of opiates, cocaine and cannabinoids in hair. Forensic Sci Int 1995;70:165-174.

Kikura R. et al. Hair analysis for drugs of abuse. IX. Comparison of Deprenyl use and methamphetamine use by hair use. Biol Pharm Bull 1995;18:267-272.

Kikura R et al. Hair analysis for drugs of abuse. XI. Disposition of benzphetamines and its metabolites in hair and comparison of benzphetamine use and methamphetamine use by hair analysis. Biol Pharm Bull 1995;18:1694-1699.

Kintz P. et al.What constitutes a positive result in hair analysis:proposal for the establishment of cut-off values. Forensic Sci Int 1995;70:3-11

Kintz P. Interlaboratory comparison of quantitative determinations of drug in hair samples. Forensic Sci Int 1995;70:105-109.

Kintz P. et al. Testing human hair and urine for anhydroecgonine methyl ester, a pyrolysis product of cocaine. J Anal Toxicol 1995;19: 479-482.

Kintz P. et al. Characterization of dextromoramide abuse by hair analysis in a denied case. Int J Leg Med. 1995;107: 269-272.

Kintz P. et al. Simultaneous determination of opiates, cocaine, and major metabolites of cocaine in human hair by GC/MS. Forensic Sci Int 1995;73:93-100.

Kintz P. et al. Testing human hair for cannabis II. Identification of THC-COOH by GC/MC-NCI as a unique proof. J Forensic Sci. 1995;40:619.

Kintz P. et al. Simultaneous determination of amphetamine, methamphetamine, 3, 4-methylenedioxamphetamine, and 3,4-methylenedioxmethamphetamine. J Chromatogr. B 1995;670: 162-166.

Kintz P. et al. [Revealing hair] [French] Ann Pharmaceut Franc 1995;53:251-255.

Kintz P. et al. Testing hair for carbamazepine in epileptic patients: Is hair investigation suitable for drug monitoring? Human Exper Toxicol 1995;14:812-815

Knight K. et al. Hair analysis: A tool to identify probationers in need of drug treatment. Fed. Probation Sept. 1995: 58-62.

Koren G. Measurement of drugs in neonatal hair: A window of fetal exposure. Forensic Sci Int 1995;70:77-82. also Harefuah 1995;129:336-338.

Magura S. et al. Measuring cocaine use by hair analysis among criminally involved youth. J Drug Issues 1995:25:683-701.

Mason A.P. et al. GCIMS detection of a single exposure to fentenyl in hair. Case Notes ToxTalk 1995;19:3.

McBay A.J. Comparison of urine and hair testing for drugs of abuse. (Letter) J Anal Toxicol. 1995;19:201-202. Cone EJ. Reply (Letter) pp. 203-204.

Mieczkowski T. A research note; the outcome of CCIMSIMS confirmation of hair assays on 93 cannabinoid (+) cases. Forensic Sci Int 1995;70:87-91.

Mieczkowski T. A Passive contamination of undercover narcotics officers by cocaine: An assessment of their exposure using hair analysis. Microgram 1995;28:193-198.

Mieczkowski T. Hair analysis as a drug detector, Oct.1995 National Institute of Justice, Washington, DC

Moeller M.R. et al. The detection of 6-monoacetylmorphine in urine, serum, and hair by GC/MS and RIA. Forensic Sci Int 1995;70; 125-135.

Nafstad P. et al. Comparison of three methods for estimating tobacco smoke exposure among children aged between 12 and 36 months. Intl J Epidemiol 1995;24:88-94.

Nakahara Y. Detection and diagnostic interpretation of amphetamines in hair. Forensic Sci Int 1995;70:135-153.

Nakahara Y et al. Hair analysis for drugs of abuse. X. Effect of physicochemical properties of drugs on the incorporation rates into hair. Biol Pharm Bull 1995;18:1223-1227.

Rothe M. et al. Solvent optimization for the direct extraction of opiates from hair samples. J Anal Toxicol. 1995;19:236-240.

Sachs H. Theoretical limits of the evaluation of drug concentrations in hair due to irregular hair growth. Forensic Sci Int 1995;70:53-61

Sallee F.R. et al. Head growth in cocaine-exposed infants: Relationship to neonate hair level. J Dev Behav Ped 1995;16:77-81.

Selavka C. et al. The determination of cocaine in hair: a review Forensic Sci Int 1995;70:i5S-l64.

Selavka C. et al. Determination of fentenyl in hair: the case of the crooked criminalist. J Forensic Sci. 1995;40:68I

Skopp G. et al. Hair analysis in the diagnosis of toxic hepatitis after Ecstacy abuse. (German) Deut Med Wochenshr 1995; 120:1165-1168.

Staub C. Analytical procedures for determination of opiate in hair: a review. Forensic Sci Int 1995;70:111-123.

Strano-Rossi S. et al Segmental hair analysis for cocaine and heroin abuse determination. Forensic Sci Tnt 1995;70:211-216.

Tagliaro F. Capillary electrophoresis: a new tool in forensic toxicology. Applications and progress in hair analysis for illicit drugs. Forensic Sci Int 1995;7093-104.

Tracqui A. et al. Hair analysis: a worthless tool for therapeutic compliance monitoring. Forensic Sci Int 1995;70:183-189

Uematsu T. at al. Time course of appearance of ofloxacin in human scalp hair after oral administration. Ther Drug Monitor 1995;17:101-103.

Uematsu T. et al. The axial distribution of nicotine content along hair shaft as an indicator of changes in smoking behavior: evaluation in a smoking cessation programme with or without the aid of nicotine chewing gum. Br. J. Clin. Pharmac. 1995;39:665-669.

Wang W. et al. Testing human hair for drugs of abuse. IV. Environmental cocaine contamination and washing effects. Forensic Sci Int 1995;70:39-51.

Wilkins D. et al. Quantitative determination of codeine and its major metabolites in human hair by gas chromatography-positive chemical ionization mass spectrometry: A clinical application. J Anal Toxicol 1995;19:269-274.

Wilkins D. et al. Quantitative analysis of THC, 11-OH-THC, and THCCOOH in human hair by negative ion chemical ionization mass spectrometry. J Anal Toxicol 1995;19:483-491.

Wilkins D. et al. Disposition of codeine in female human hair after multple-dose administration. J Anal Toxicol 1995;19: 492-498.

The following papers are from a workshop conducted on May 13,1993 at NIDA which were published in 1995 in, 'Hair Testing for Drugs of Abuse' edited by E. Cone, M. Welch, B Babecki, NIH Publication No. 95-3727:

Kidwell DA et al. Mechanism of incorporation of drugs in hair and the interpretation of hair analysis data. Pp. 19-90

Henderson GL et al. Analysis of hair for cocaine. Pp. 91-120.

Cone EJ et al. How environmental drug exposure can affect hair testing for drugs. pp. 121-132.

Welch MJ et al. lnterlaboratory studies on the analysis of hair for drugs of abuse: Results from three exercises. Pp. 133-147.

Baumgartner WA et al. Hair analysis for drugs of abuse: Probative features of hair testing. Pp. 1 48-1 85.

Kintz P. Testing human hair for opiates and cocaine by GC/MS after acid or enzyme hydrolysis. Pp. 1 86-1 9 5.

Sachs H et al. Quantitative results of drugs in hair using different extraction methods. Pp.1 96- 21 1.

Pichini S et al. Analysis of nicotine and cotinine in human hair by HPLC and comparative determination with RIA. Pp. 212-224.

Tagliaro F et al. Capillary electrophoresis: A novel tool for toxicological Investigation: Its potential in the analysis of body fluids and hair. Pp. 225-247.

Selavka CM et al. Casework findings and a practical discussion of rinsing procedures in forensic drug testing. Pp.248-276.

Cirimele V et al. Comparison of different extraction procedures for drugs in hair of drug addicts. Pp. 277-288.

Miller ML at al. Research at the Federal Bureau of Investigation in hair analysis for drugs of abuse. Pp. 289-31 1.

Moeller MR et al, Hair analysis for opiates in forensic cases. Pp. 312-332.

Uematsu T et al. Human scalp hair as biopsy material suitable for quantitative analysis in therapeutic drug monitoring. pp. 333-346.

Klein J et al. Neonatal hair analysis: A tool for the assessment of in utero exposure to drugs. Pp.347- 361.

Katikaneni et al. Neonatal hair analysis for benzoylecgonine: A market for gestational cocaine exposure, growth at birth, and neurodevelopment based on short-term followup (4 to 6 months). Pp. 362-398.

Back to Index

1996

The following papers are from: Drug Testing in Hair, edited by Pascal Kintz, published by CRC Press 1996:

Baumgartner W.A. et al. Hair analysis for organic analytes: methodology, reliability issues and field studies. pp. 223-265.

Ciremele V. Cannabis and amphetamine determination in human hair. pp.181-189.

Cone E.J. et al. The potential for bias in hair testing for drugs of abuse. pp. 69-93.

Garside D. et al Determination of cocaine and opiates in hair. pp. 151-180.

Huestis M.A. Technical and legal aspects of drug s of abuse testing in hair. pp. 1-15.

Kidwell D. et al. Environmental exposure- the stumbling block of hair testing. pp. 17-68.

Kintz P. Clinical applications of hair analysis. pp. 267-277.

Mangin P. Drug analysis in nonhead hair. pp. 279-187.

Moeller M.R., The analytical tools for hair testing. pp. 95-120.

Sachs H. Forensic applications of hair analysis. pp. 211-222.

Staub C. et al. Importance of supercritical fluid extraction (SFE) in hair analysis. 121-149.

Tracqui A. Unusual drugs in hair. 191-210

Other 1996 Articles

Callaghan RR et al. An assessment of the routes of incorporation of opiates into beard hair after a single oral dose of codeine. Ther Drug Monit. 1996;6:724-726

Chiarotti M. et al. Evaluation of cocaine use during pregnancy through toxicological analysis of hair. J Anal Toxicol 1996;20:555-558.

Cirimele V. et al. Testing human hair for cannabis III. Rapid screening procedure for the simultaneous identification of tetrahydrocannabinol, cannabinol, and cannabidiol. J Anal Toxicol 1996;20:13-16.

Cirimele V. et al. Determination of chronic flunitrazepam abuse by hair analysis using GC-MS-NCI. J Anal Toxicol 1996;20:596-598.

Cirimele V et al. Detection and quantitation of lorazepam in human hair by GC/MS/NCI in a case of traffic accident. Int J Legal Med 1996;108:265-267.

Cirimele V et al. Comparison of different extraction procedures for drugs in hair of drug addicts. Biomedical Chromatography 1996;10:179-182

Cone E. J. Mechanisms of drug incorporation in hair. Ther Drug Monit. 1996;18:438-443.

Eliopoulus C et al. Validation of self-reported smoking by analysis of hair for nicotine and cotinine. Ther Drug Monit. 1996; 18:532-536.

Fujii J et al. Examination of stability of anticonvulsants in a protease solution and assay of anticonvulsants in hairs. Biological Pharmaceut Bull 1996; 12:1614-1617.

Gleixner A. et al. Detection of the anabolic beta 2 adrenoceptor against clenbuteral in human scalp hair by HPLC/EIA. Clin Chem 1996;42:1869-1871.

Goulle J.P. et al. A new tool for biological study: Hair analysis. Value in medical practice. (French). Revue de Med. Interne 1996;17:826-835.

Green SJ et al. Evidence of saturable incorporation of methadone into rat hair; relationship among oral dose, plasma concentration and hair content. Ther Drug Monit. 1996; 6:710-713.

Green S et al. The effect of hair color on the incorporation of methadone into rat hair. J Anal Toxicol 1996;20:121-123.

Knight K. et al. Passive smoking in children: Racial differences in systematic exposure to cocaine by hair and urine analysis. Chest 1996;109:446-450

Henderson G. et al. Incorporation of isotopically labeled cocaine and metabolites into human hair: l. Dose-response relationships. J Anal Toxicol 1996;20:1-12.

Huestis M.A. Judicial acceptance of hair tests for substances of abuse in the US courts: scientific, forensic and ethical aspects. Ther Drug Monit. 1996;18:456-459.

Hold K.M. et al. Detection of stanozolol in hair by negative ion chemical ionization mass spectrometry. J Anal Toxicol 1996;20: 345-349.

Joseph R.E. et al. In vitro binding studies to hair: Influence of melanin and lipids on cocaine binding in Caucasoid and africoid hair. J Anal Toxicol 1996;20:338-344.

Jurado C. et al. Hair testing for cannabis in Spain and France: Is there a difference in consumption? J Anal Toxicol 1996;20:111-11S.

Kauert G. et al. Concentrations of THC, cocaine and 6-MAM in hair of drug abusers. Intnl J Legal Med 1996; 108, 294.

Kelly K.S. et al. Detection of misreported drug use in forensic populations: An overview of hair analysis. Bull Am Acad Psychiatry Law 1996;24:85-94.

Kintz P. et al. Drug testing in addicts: A comparison between urine, sweat, and hair. Ther Drug monit. 1996;18:450-455.

Kintz P. et al. Testing human hair for clozapine (letter) Ann Biol Clin (Paris) 1996;54:317-318.

Kintz P. et al. Hair analysis for nordiazepam and oxazepam by GC-negative ion MS. J Chromagr B i996; 677:241.

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