Medical Review Officer
Manual
for Federal Agency Workplace Drug Testing Programs
November 1, 2004 (Effective Date)
This manual provides additional guidance to supplement
the medical review officer requirements contained in the Mandatory Guidelines
for Federal Workplace Drug Testing Programs that were published in the Federal
Register on April 13, 2004 (69 FR 19644), with a November 1, 2004,
implementation date.
Note: This manual does not apply to specimens collected
under the Department of Transportation Procedures for Transportation Workplace
Drug and Alcohol Testing Programs (49 CFR Part 40).
Previous Versions of this Manual are Obsolete
Table of Contents
Chapter
Chapter 1. The Medical Review
Officer (MRO)
The final review of results is an essential component
of any drug testing program. A positive laboratory test result does not
automatically identify an employee or job applicant as an illegal drug user,
nor does a laboratory result of invalid, substituted, or adulterated
automatically identify specimen tampering. An individual with a detailed
knowledge of possible alternative medical explanations must interpret
non-negative results in the context of information obtained from the donor
interview. HHS requires the Medical Review Officer (MRO) to fulfill this
important function.
The HHS Mandatory Guidelines define an MRO as a
licensed physician holding either a Doctor of Medicine (M.D.) or Doctor of
Osteopathy (D.O.) degree who has:
-
Knowledge about and clinical experience in controlled
substance abuse disorders,
-
Detailed knowledge of alternative medical
explanations for laboratory positive drug test results,
-
Knowledge about issues relating to adulterated and
substituted specimens, and
-
Knowledge about possible medical causes for specimens
reported as having an invalid result.
MRO training programs are available from various
professional organizations to ensure that MROs are familiar with current
regulations and receive the latest information on interpreting test results.
Although HHS does not require formal certification for MROs at the present
time, training courses have served a very important role in providing
continuing education for MROs.
The MRO serves as the common point of contact between
all parties involved in a drug test (i.e., the donor, the collector, the
laboratory, and the Federal agency's designated representative). The MRO may be
an employee or a contractor for a Federal agency; however, the following
restrictions apply:
-
The MRO must not be an employee or agent of or have
any financial interest in the laboratory for which the MRO is reviewing drug
testing results, and
-
The MRO must not derive any financial benefit by
having an agency use a specific drug testing laboratory or have any agreement
with the laboratory that may be construed as a potential conflict of interest.
The purpose of these prohibitions is to prevent any
arrangement between a laboratory and an MRO that would prevent the MRO from
reporting a problem identified with a laboratory's test results or testing
procedures.
The MRO has the following responsibilities:
-
Determine that the information on the Federal Drug
Testing Custody and Control Form (Federal CCF) is correct and complete,
-
Interview the donor when required,
-
Make a determination regarding the drug test results,
-
Report the result to the Federal agency, and
-
Maintain records and confidentiality of the
information.
HHS recommends that each MRO use the guidance
contained in this manual to ensure consistency and to improve the overall
quality of the review process.
The following professional organizations offer courses
and information for licensed physicians who are interested in the MRO
specialty:
American College of Occupational and Environmental
Medicine (ACOEM)
1114 North Arlington Heights Road
Arlington Heights, IL 60004-4770
Telephone: 847- 818-1800
Fax: 847-818-9266
www.acoem.org
American Society of Addiction Medicine (ASAM)
4601 North Park Avenue, Upper Arcade #101
Chevy Chase, MD 20815
Telephone: 301- 656-3920
Fax: 301-656-3815
www.asam.org
American Association of Medical Review Officers
(AAMRO)
P.O.Box 12873
Research Triangle Park, NC 27709
Telephone: 1-800-489-1839
Fax: 919-490-1010
www.aamro.com
Note: The listing of these organizations is not
an endorsement by the Federal government.
Chapter 2. The Federal Drug
Testing Custody and Control Form
Federal agencies are required to use the Office of
Management and Budget (OMB) approved Federal CCF for their agency workplace
drug testing programs.
The following employers are prohibited from
using the Federal CCF:
-
Private-sector companies
-
States
-
Department of Justice programs
-
Non-DOT testing conducted by DOT-regulated employers
The Federal CCF is usually provided by the laboratory
that will test the specimen and is also available from other sources (e.g.,
forms suppliers, collectors, MROs).
A sample of the Federal CCF is on the SAMHSA website
at http://workplace.samhsa.gov/. All
discussions in this manual refer to this version of the Federal CCF (OMB Number
0930-0158).
The Federal CCF consists of 5 copies that are
distributed by the collector as follows:
Copy 1 - Laboratory Copy - sent to the laboratory with
the specimen bottle(s)
Copy 2 - MRO Copy - sent to the MRO
Copy 3 - Collector Copy - retained by the collector
Copy 4 - Employer Copy - sent to the Federal agency
Copy 5 - Donor Copy - given to the donor when the
collection process is complete
Each Federal CCF is printed with a unique specimen
identification number. The Federal CCF includes labels with the same ID number
that the collector places on the specimen bottle(s) to link the specimen to
information on the CCF. Information that is pre-printed or written on the
Federal CCF includes:
-
Name, address, and contact information for the
collection site, collector, Federal agency/employer, MRO, and testing
laboratory,
-
Donor identifying information,
-
Reason for test, and
-
Test(s) to be performed.
The collector initiates the chain of custody
documentation for the specimen using the Federal CCF. The term "chain of
custody" refers to documentation of all handling of a specimen. Chain of
custody documents provide evidence that the specimen was secure and its
integrity was maintained from the time of collection to its final disposition.
The Federal CCF is sealed and shipped with the
specimen bottle(s) to the laboratory. The laboratory staff member who receives
and processes the specimen for testing (i.e., the accessioner) verifies the
information that is on the bottle(s) and on the Federal CCF and signs the
Federal CCF. Thereafter, laboratory staff members document the chain of custody
of the specimen and all aliquots taken for testing using internal laboratory
forms.
The laboratory must be in a secure facility, with
access limited to authorized personnel. Individual areas within the laboratory
(e.g., receiving/accessioning area, testing areas, sample preparation area,
specimen storage areas) are usually separately secured, to limit access to
staff with job duties in the area. All visitors to secured areas must be
escorted and their access must be documented.
Certified laboratories must ensure the security and
integrity of regulated specimens, and follow strict chain of custody procedures
to provide a forensically acceptable record of the specimen's handling. This
requires that all specimens be kept in secured storage or in the line of sight
custody of an authorized individual, with appropriate chain of custody entries
(i.e., signature, date, and action/purpose of each custody transfer) made at
the time of actions. In addition, laboratories are required to maintain the
confidentiality of donor information by restricting access to records of
regulated specimens.
When a specimen's testing is complete, the certifying
scientist at the laboratory reviews all data and associated documentation for
the specimen including the Federal CCF. The certifying scientist annotates the
specimen's results by marking the appropriate boxes on the Federal CCF, and
including any additional comments concerning the specimen's testing or
processing on the "Remarks" line. By signing the certification statement on the
Federal CCF, this individual attests that the specimen was handled and tested
in accordance with Federal requirements.
For non-negative results, the laboratory must
send the laboratory copy of the Federal CCF (Copy 1) or a legible image of Copy
1 to the MRO. The laboratory is allowed to send a computer-generated report in
addition to the Federal CCF.
-
The copy of the Federal CCF (Copy 1) will be marked
with one or more of the following non-negative results:
-
Positive for one or more drugs,
-
Adulterated (with the adulterant or pH value recorded
on the "Remarks" line),
-
Substituted (with the creatinine and specific gravity
values recorded on the "Remarks" line), or
-
"Invalid result" (with the reason for the invalid
result recorded on the "Remarks" line).
-
These are separate results. For example,
"invalid result" does not refer to the drug(s)/drug metabolite(s) marked
positive. The MRO should contact the laboratory if there is any confusion about
the reported results.
For negative results, the laboratory is allowed
to report the results using a computer-generated report (i.e., the completed
Federal CCF is retained by the laboratory).
Chapter 3. Urine Drug Testing
A Federal agency may collect urine specimens using
either a single specimen collection procedure or a split specimen collection
procedure. The collector prepares a split specimen by pouring the urine from
the collection container into two bottles, which are then labeled as the A
Bottle and the B Bottle. All specimens (including all aliquots taken from the
original specimens) are handled using strict chain of custody procedures to
provide a clear record of each specimen's handling from the time it was
collected until final disposition by the laboratory.
HHS-certified laboratories may routinely only test
Federal agency specimens for amphetamines, marijuana, cocaine, opiates, and
phencyclidine. However, testing for an additional drug may occur for one of the
following reasons:
-
There is reasonable suspicion/cause or a
post-accident incident for which testing for another drug listed in Schedule I
or II of the Controlled Substances Act is justified (see Section B, Drug
Information, below); or
-
A Federal agency was granted a waiver by the
Secretary of HHS to routinely test its employees for another drug or drug
class.
For any circumstance where testing for an additional
drug is justified or authorized, the Federal agency must prepare a memorandum
explaining why the specimen is being tested for the additional drug. The
memorandum is given to the collector and the collector then marks the "Other"
box in Step 1 on the Federal CCF and specifies the name of the drug(s) to be
tested. The memorandum from the Federal agency is attached to the Federal CCF
when the urine specimen is transferred to the laboratory. If the memorandum is
not provided to the laboratory, the laboratory must not test for the additional
drug noted on the Federal CCF.
For forensic as well as scientific acceptability,
laboratories are required to perform initial and confirmatory tests on a
specimen to support a non-negative result. Initial drug and specimen validity
tests are performed on all specimens. Those specimens that have negative
initial drug test results and acceptable initial specimen validity test results
are reported as negative. Specimens that are presumptive drug positive,
substituted, or adulterated are subjected to confirmatory testing using a
different test method that is usually more specific than the initial test.
The donor is given the opportunity to request a retest
when his or her specimen is reported as positive, substituted, or adulterated.
The retest (i.e., an aliquot of the single specimen collection or Bottle B of a
split specimen collection) is performed at a second certified laboratory.
If the donor chooses not to request specimen
retesting, a Federal agency may have a single or split specimen retested as
part of a legal or administrative proceeding to defend an original positive,
adulterated, or substituted result.
Laboratories are required to maintain the following
specimens in a secure frozen storage area for at least one year after reporting
the result:
-
Drug positive specimens
-
Substituted specimens
-
Adulterated specimens
-
Invalid specimens
-
Split specimens (B Bottles) of the primary specimens
listed above
-
Any specimens or specimen aliquots received from
another laboratory for retesting
A Federal agency may request the laboratory to retain
a specimen for a longer period (e.g., specimens under legal challenge).
Laboratories may discard rejected specimens after
reporting them as rejected to the MRO.
A. Test Methods
An MRO is not required to be as technically
knowledgeable of the analytical procedures and data as a laboratory certifying
scientist. However, the MRO must know what tests were used to generate the
specimen results that he or she reviews and should understand the general
scientific principles of the technologies.
Certified laboratories are required to use immunoassay
for initial drug tests and to use gas chromatography/mass spectrometry
(GC/MS) for confirmatory drug tests.
Immunoassay
Immunoassays are immunochemical testing methods that use antigen activity to
identify drug analytes. Antibodies to the drug analyte (i.e., the antigen) are
produced. A known amount of the antibody is added to a specimen along with drug
that has been labeled with an enzyme or radioactive label. The drug in the
specimen competes with the labeled drug for the antibody, to form an
antigen-antibody complex. Various methods are used to measure the amount of
drug present in the specimen. Immunoassays are used as initial drug tests, the
preliminary test to identify presumptive positive specimens. The method is not
specific enough to use as a confirmatory test. For example, many structurally
similar drugs may cross-react with an immunoassay reagent, giving a positive
result. Specimens that are positive by immunoassay are tested using GC/MS as a
confirmatory test, to specifically identify and quantitate the drug or drug
metabolite.
Table 1 provides brief descriptions of common immunoassays used for
drugs of abuse.
Gas Chromatography/Mass Spectrometry (GC/MS)
Gas chromatography is a chromatographic technique for separating and analyzing
mixtures of chemical substances in a gas or vapor mobile phase by adsorption on
a stationary phase. GC/MS is a combined technique coupling a mass spectrometer
(MS) with a GC instrument. Urine specimens must undergo a specimen preparation
process (i.e., extraction) prior to GC/MS analysis. After the GC has separated
the analytes in a specimen, the specimen enters the MS, which identifies and
quantitates the separated analytes. The MS creates charged particles (ions) and
separates them according to their mass-to-charge (m/z) ratios. The ions form
unique mass spectra, which are used to identify analytes.
While the Guidelines do not specify the methods to be
used for initial and confirmatory specimen validity tests,laboratories
are required to use a pH meter for the initial and confirmatory pH tests and a
refractometer measuring to at least four decimal places for the initial and
confirmatory specific gravity tests. Laboratories must use appropriate,
validated methods for all specimen validity tests.
Table 2 provides brief descriptions of some
methods that may be used for specimen validity tests.
B. Drug Information
The Federal Government classifies controlled
substances under 5 schedules established under the Controlled Substances Act
(CSA):
Schedule I:
-
The drug or other substance has a high potential for
abuse.
-
The drug or other substance has no currently accepted
medical use in treatment in the United States.
-
There is a lack of accepted safety for use of the
drug or other substance under medical supervision.
Schedule II:
-
The drug or other substance has a high potential for
abuse.
-
The drug or other substance has a currently accepted
medical use in treatment in the United States or a currently accepted medical
use with severe restrictions.
-
Abuse of the drug or other substances may lead to
severe psychological or physical dependence.
Schedule III:
-
The drug or other substance has a potential for abuse
less than the drugs or other substances in schedules I and II.
-
The drug or other substance has a currently accepted
medical use in treatment in the United States.
-
Abuse of the drug or other substance may lead to
moderate or low physical dependence or high psychological dependence.
Schedule IV:
-
The drug or other substance has a low potential for
abuse relative to the drugs or other substances in schedule III.
-
The drug or other substance has a currently accepted
medical use in treatment in the United States.
-
Abuse of the drug or other substance may lead to
limited physical dependence or psychological dependence relative to the drugs
or other substances in schedule III.
Schedule V:
-
The drug or other substance has a low potential for
abuse relative to the drugs or other substances in schedule IV.
-
The drug or other substance has a currently accepted
medical use in treatment in the United States.
-
Abuse of the drug or other substance may lead to
limited physical dependence or psychological dependence relative to the drugs
or other substances in schedule IV.
The President's Executive Order 12564 defines "illegal
drugs" as those under Schedule I or Schedule II. The U.S. Drug Enforcement
Administration (DEA) enforces the provisions of the CSA.
Cannabinoids (Marijuana)
1. Background
Cannabinoid-containing compounds come from the hemp
plant, Cannabis sativa. The principal psychoactive agent in cannabinoids is
delta 9 tetrahydrocannabinol (THC). Certified laboratories are required to use
confirmatory testing for cannabinoids that specifically identifies delta-9-THC.
Cannabinoid-containing compounds are found in two
forms, marijuana and hashish. Marijuana is a mixture of crushed leaves,
flowers, and sometimes the stems of the cannabis plant. Hashish contains the
dried resinous secretions of the cannabis plant and, in general, has a higher
concentration of THC than marijuana.
Marijuana is a Schedule I drug. Medical marijuana is a
controversial issue, and there has been some scientific evidence that smoked
marijuana is beneficial for patients with debilitating symptoms such as
unmanageable pain and vomiting. However, use of marijuana is not an acceptable
alternative medical explanation for a positive confirmed drug test result in
federally-regulated drug testing programs.
Dronabinol is chemically synthesized
delta-9-tetrahydrocannabinol (THC). It is the sole pharmaceutical source of THC
and is available as Marinol® (Roxane Laboratories). The drug has psychoactive
effects that may present safety issues.
Nabilone (Cesamet®) is a synthetic cannabinoid
available in Europe. This drug does not metabolize to delta-9-THC. Therefore,
the use of Nabilone is not an acceptable medical explanation for a positive
confirmed drug test.
Cannabinoids produce a pleasant euphoria or "high" and
a sense of relaxation and well-being that is commonly followed by drowsiness.
The initial psychoactive effects of smoking THC occur within minutes, reach a
peak within 10-30 minutes and may persist for 2-4 hours. Intoxication
temporarily impairs concentration, learning, and perceptual motor skills.
Reduced functional ability lasts for at least 4-8 hours after a dose of
marijuana. Psychomotor performance may be impaired long after the acute
subjective effects have ended. In one study, experienced pilots demonstrated
impaired performance in a flight simulator for 24 hours after a dose, long
after the subjective "high" had disappeared9. Functional impairment
is not well understood in cases of prolonged, heavy marijuana use, because
behavioral and physiological tolerance develops.
In addition to tolerance, a mild abstinence syndrome
may follow abrupt termination of very high dose, chronic marijuana use.
Withdrawal signs include irritability, sleep disturbance, diminished appetite,
gastrointestinal distress, salivation, sweating, and tremors. Marijuana
abstinence syndromes are uncommon when used at the doses usually taken in this
country.
Routes of administration:
-
Marijuana - smoking (preferred), and oral (i.e.,
eating)
-
Hashish - smoking (preferred), and oral (i.e.,
eating)
2. Metabolism and Excretion
Cannabinoids are usually smoked. Trans-pulmonary
absorption occurs quickly and causes a direct psychoactive response in the
brain. Cannabinoids are sometimes eaten because the drug also is absorbed
through the gastrointestinal tract; however, gastro-intestinal absorption
occurs much more slowly. THC is distributed into different parts of the body
where it is metabolized, excreted, or stored. The THC that is stored in fatty
tissue gradually reenters the blood stream at very low levels, permitting
metabolism and eventual excretion. THC is metabolized extensively in the liver
and the major metabolite is 11-nor-Delta9- tetrahydrocannabinol 9
carboxylic acid (delta-9 THCA).
The immunoassay procedures detect multiple metabolites
of marijuana, while the GC/MS procedures specifically identify and quantitate
delta-9 THCA. To be reported positive under the HHS Guidelines, a specimen must
test positive at or above the 50 ng/mL cutoff for the initial test and have a
concentration of delta-9 THCA that is equal to or greater than the 15 ng/mL
confirmatory cutoff level. Infrequent marijuana use may cause positive initial
test results for 1-5 days2. With repeated smoking, THC accumulates
in fatty tissue. Chronic smokers slowly release THC over a longer time and may
continue to produce detectable levels of drug for longer periods of time.
Cocaine
1. Background
Cocaine is an alkaloid from the coca plant that is
usually sold as cocaine hydrochloride, a fine, white crystalline powder.
"Freebasing" is a method used to chemically alter cocaine hydrochloride to
remove the hydrochloride salt. "Crack" is one form of free base cocaine that
has become popular in recent years. It is sold as small lumps or shavings and
is the product of a manufacturing process that uses sodium bicarbonate or
ammonia rather than a flammable solvent. Because it survives high temperatures,
crack is smoked, resulting in absorption into the bloodstream that is as rapid
as injection. Cocaine is metabolized within hours of administration and;
therefore, the Federal drug testing program requires analysis for cocaine as
its major metabolite benzoylecgonine.
Cocaine has only a limited legal use in the United
States as a topical anesthetic in ear, nose, and throat surgery. It is a widely
used drug of abuse and is classified as a Schedule II drug.
Cocaine produces psychomotor and autonomic stimulation
with a euphoric subjective "high." Larger doses may induce mental confusion or
paranoid delusions. Serious overdoses cause seizures, respiratory depression,
cardiac arrhythmias, and death.
Short-term tolerance (tachyphylaxis) develops when
several doses of cocaine are administered over a brief period. Among chronic
users, the stimulant effect may seem progressively weaker, and exhaustion,
lethargy, and mental depression appear. Cocaine abusers often report vocational
impairment due to exhaustion even though they do not use the drug at work.
Patients withdrawing from cocaine experience moderate
lethargy and drowsiness, severe headaches, hyperphagia, vivid dreams, and some
mental depression. These symptoms usually subside within a few days to a few
weeks.
Routes of administration:
-
Intranasal (i.e., snorting) is the most common
-
Smoking the "freebase" or "crack" form of the drug
-
Intravenous injection
2. Metabolism and Excretion
Cocaine is rapidly and extensively metabolized by
liver and plasma enzymes to its major metabolite benzoylecgonine.
Benzoylecgonine is more persistent and can usually be detected for up to 2 days
after a single dose. Cocaine and benzoylecgonine are not significantly stored
in the body. Therefore, even after heavy, chronic use, urine specimens will be
negative when collected a few days after last use.
Opiates
1. Background
The term "opiate" specifically refers to natural
alkaloids extracted from the opium poppy. The term "opioid" refers to synthetic
opiates and opiate-like drugs in addition to the naturally occurring opiates.
Opioids are classified as narcotics. The Federal agency drug testing program's
focus is on illicit use of morphine, codeine, and heroin:
-
Morphine - is the most abundant naturally occurring
opiate and is considered the prototype of the opioid class of drugs. Morphine
is available as a prescription drug (Schedule II) and is used primarily for its
potent analgesic properties.
-
Codeine - can be naturally occurring; however, it can
also be synthesized chemically by 3-O-methylation of morphine. Codeine
medications are available by prescription and over-the-counter (Schedule III,
Schedule IV, and Schedule V), depending on concentration and preparation.
Codeine is commonly used in analgesic, antitussive, and anti-diarrheal agents.
-
Heroin (diacetylmorphine) - is a semisynthetic opiate
obtained by reacting natural morphine with acetic acid. Heroin has no
legitimate medical use in the United States and is only available illegally
(Schedule I). Heroin is not easily detected in urine and therefore usage is
determined by detection of its intermediate metabolite 6-acetylmorphine (6-AM).
Cognitive and psychomotor performance can be impaired
by opiates, although the duration and extent of impairment depend on the type
of opiate, the dose, and the experience and drug history of the user. Ingestion
of low to moderate amounts produces a short lived feeling of euphoria followed
by a state of physical and mental relaxation that persists for several hours.
Opioid intoxication may cause meiosis, a dull facies, confusion or mental
dullness, slurring of speech, drowsiness, or partial ptosis (i.e., nodding, the
head drooping toward the chest and then bobbing up).
It is common for opioid abusers to develop tolerance
and therefore continually increase the dose taken in an attempt to maintain the
euphoric effect. All opiates are physically and psychologically addictive, and
produce withdrawal symptoms that differ in type and severity. Flu-like symptoms
are common during opiate withdrawal (e.g., watery eyes, nausea and vomiting,
muscle cramps, and loss of appetite).
Routes of administration:
-
Morphine - injection, intranasal (i.e., snorting),
oral (i.e., tablets), and smoking
-
Codeine - injection and oral (i.e., tablets, elixir)
-
Heroin- intravenous injection, intranasal (i.e.,
snorting), and smoking
Additional issues regarding opioids:
-
Poppy seeds are a significant dietary source of
codeine and/or morphine.
-
In December 1998, HHS revised the Mandatory
Guidelines for Federal Workplace Drug Testing Programs to increase the initial
testing and confirmatory cutoffs for opiates (i.e., from 300 ng/ml to 2000
ng/ml) and require laboratories to test all morphine positive specimens for
heroin metabolite (6-AM). These measures were taken to eliminate most specimens
that test positive due to poppy seed ingestion or due to the use of legitimate
morphine or codeine medication.
-
Synthetic or semi-synthetic narcotics do not
metabolize to codeine, morphine, or 6-acetylmorphine. These include, but are
not limited to:
-
alphaprodine (Nisentil®)
-
hydromorphone (Dilaudid®)
-
oxymorphone (Numorphan®)
-
hydrocodone (Hycodan®, Lorcet-HD®, Vicodin®)
-
dihydrocodeine (Synalgos®)
-
oxycodone (Percodan®, Percocet®, Tylox®)
-
propoxyphene (Darvon®)
-
methadone (Dolophine®)
-
meperidine (Demerol®)
-
fentanyl (Duragesic®, Sublimaze®)
-
pentazocine (Talwin®)
-
buprenorphine (Buprenex®, Subutex®)
Table 3 provides a representative sample of the
prescription and non-prescription products that contain codeine or morphine.
Note: Further information regarding the interpretation
and reporting of opiates is found in the Interpretation and Result Verification
Section (i.e., Chapter 5, Section C.)
2. Metabolism and Excretion
Morphine is rapidly absorbed and excreted as:
-
unchanged morphine
-
glucuronide conjugates
-
morphine-3-glucuronide (primary metabolite)
-
morphine-6-glucuronide
Morphine and its metabolites can be detected in urine
up to about four days after its use. Morphine is not metabolized to codeine.
Codeine (methylmorphine) is also rapidly absorbed and is excreted as:
-
unchanged codeine
-
morphine
-
glucuronide conjugates
-
codeine-6-glucuronide
-
morphine-3-glucuronide
-
morphine-6-glucuronide
The presence of both codeine and morphine in urine
indicate the recent use of codeine; however, morphine alone may be detected as
a remnant of codeine that has been completely metabolized.
Heroin (diacetylmorphine) is deacetylated to its
primary metabolite 6-AM (also known as 6-monoacetylmorphine, 6-MAM) within
minutes of administration. Therefore, heroin itself is rarely detected in
urine. 6-AM is mostly likely to be detected within the first 24 hours
post-administration because of its rapid metabolism to morphine. Codeine may be
found in the urine of heroin users as a result of codeine present as a
contaminant in the morphine used to synthesize the heroin.
Amphetamines
1. Background
Amphetamine and methamphetamine are substances
regulated under the Controlled Substances Act as Schedule II stimulants. Both
drugs have been used for treating attention deficit disorder in children,
obesity, and narcolepsy.
Amphetamine and methamphetamine are central nervous
system stimulants that initially produce euphoria, a feeling of well-being,
increased self-esteem and appetite suppression followed by restlessness and
irritability. A single therapeutic dose often enhances attention and
performance, but exhaustion eventually occurs and performance deteriorates as
the effects wear off. Frequently, repeated high dose use produces lethargy,
exhaustion, mental confusion, and paranoid thoughts.
Tolerance can develop to the effects of amphetamine
and methamphetamine. A typical therapeutic dose is 5 milligrams. Individuals
who abuse these drugs are reported to inject up to one gram in a single
intravenous dose. Physical dependence is modest. Lethargy, drowsiness,
hyperphagia, vivid dreams, and some mental depression may persist for a few
days to several weeks after abrupt termination of repeated high doses.
Amphetamine and methamphetamine exist in two isomeric
structural forms known as enantiomers. Enantiomers are non -superimposable
mirror images. The two isomers of each substance are designated as d- (dextro)
and l- (levo), indicating the direction in which they rotate a beam of
polarized light. As do many pharmacological enantiomers, the d- and l- isomers
have distinct pharmacological properties. In this case, the d- isomer of each
substance has a strong central nervous system stimulant effect while the l-
isomer of each substance has primarily a peripheral action. Illegally
manufactured amphetamine and methamphetamine are principally found as the
d-isomer. However, significant amounts of the l- isomer of each substance may
be present depending on the starting materials used by the clandestine
laboratories.
Routes of administration:
-
Amphetamine - oral (i.e., tablets or capsules),
intravenous injection, smoking, and intranasal (i.e., snorting)
-
Methamphetamine - oral (i.e., tablets or capsules),
intravenous injection, smoking, and intranasal (i.e., snorting)
Table 4 provides a representative sample of products containing
amphetamines.
2. Metabolism and Excretion
Nearly half of a methamphetamine dose is recovered
from urine unchanged. A small percentage is demethylated to amphetamine and its
metabolites. The excretion rate of methamphetamine is also increased when urine
is acidic.
Amphetamine is excreted as both unchanged amphetamine
and as hydroxylated metabolites. Typically, about one quarter of an
administered dose is excreted as unchanged amphetamine, but this varies widely
with urinary pH; the drug stays in the body longer when urine is alkaline,
allowing re-absorption and thus allowing more of it to be metabolized. In 24
hours, about 80 percent of a dose will be excreted if urine is acidic, while
less than half is excreted if urine is alkaline.
A single therapeutic dose of amphetamine or
methamphetamine can produce a positive urine for about 24 hours depending upon
urine pH and individual metabolic differences. High dose abusers may continue
to generate positive urine specimens for 2 to 4 days after last use.
Generally, the amphetamine/methamphetamine result
reported by the laboratory does not indicate the specific enantiomer because
the laboratory procedure is set up to only identify and quantitate the presence
of amphetamine and/or methamphetamine. In order to determine which enantiomer
is present, an additional analysis must be performed.
The enantiomer identification may be useful in
determining if a donor has been using a Vicks Inhaler®, a prescription
medication, or abusing an illegal drug; however, the presence of the l- isomer
of either amphetamine or methamphetamine does not by itself rule out illegal
use.
Phencyclidine
1. Background
Phencyclidine (PCP), an arylcyclohexylamine, was first
synthesized in the 1950's as a general anesthetic. Street names include Angel
Dust, Crystal, Killer Weed, Supergrass, and Rocket Fuel. PCP's synthesis is
relatively simple for clandestine laboratories. Phencyclidine's use as a human
anesthetic was discontinued because it produced psychotic reactions
(i.e.,"emergence delirium"), but the drug remains in use as a veterinary
tranquilizing agent. PCP is currently a Schedule II controlled substance.
PCP has a variety of effects on the central nervous
system. Intoxication begins several minutes after ingestion and usually lasts
eight hours or more. PCP is well known for producing unpredictable side
effects, such as psychosis or fits of agitation and excitability. The severe
debilitating physical and psychological effects of PCP abuse and the extremely
unpredictable behavior caused by the drug clearly have drastic effects on
performance.
Intoxication may result in persistent horizontal
nystagmus, blurred vision, diminished sensation, ataxia, hyperreflexia, clonus,
tremor, muscular rigidity, muteness, confusion, anxious amnesia, distortion of
body image, depersonalization, thought disorder, auditory hallucinations, and
variable motor depression or stimulation, which may include aggressive or
bizarre behavior.
Ketamine is the only analog of PCP that has any
legitimate use. It is currently used in veterinary treatment. Ketamine does not
cross-react with PCP initial or confirmatory testing.
Routes of administration:
-
Smoking (preferred)
-
Oral
-
Intranasal (i.e., snorting)
-
Intravenous injection
2. Metabolism and Excretion
PCP is well absorbed by any route and is excreted as
unchanged PCP and as conjugates of hydroxylated PCP. About 10 to 15 percent of
the PCP dose is excreted in the urine as unchanged drug. PCP is a weak base
which concentrates in acidic solutions in the body. Because of gastric acidity,
PCP repeatedly re-enters the stomach from plasma, and is re-absorbed into
plasma from the basic medium of the intestine.
Generally, PCP is considered detectable in urine for
several days to several weeks depending on the frequency of use.
C. Adulterant Information
"Adulterated" is the term used for a specimen that has
been altered by the donor in an attempt to defeat the drug test. The goal is to
affect the ability of the laboratory to properly test the specimen for drugs
and/or to destroy any drug or drug metabolite that may be present in the
specimen. Many substances can be used to adulterate a urine specimen in vitro,
including common household products, commercial chemicals, and commercial
products developed specifically for drug test specimen adulteration.
Adulterants are therefore readily available, may be easily concealed by the
donor during the collection procedure, and can be added to a urine specimen
without affecting the temperature or physical appearance of the specimen. To
identify adulterated specimens, HHS requires certified laboratories to perform
a pH test and a test for one or more oxidizing compounds on all regulated
specimens. Laboratories are also allowed to test regulated specimens for any
other adulterant, providing they use initial and confirmatory tests that meet
the validation and quality control requirements specified by the HHS
Guidelines.
An adulterant may interfere with a particular test
method or analyte, but not affect others. For example, an adulterant may cause
false negative marijuana (cannabinoids) results using a particular immunoassay
reagent, but not affect the test results for other drugs. The same adulterant
may not affect the test results obtained using a different immunoassay reagent
or different immunoassay method. It is also possible for an adulterant to cause
false positive drug test results, rather than the intended false negative. The
initial drug test required for Federal workplace programs (immunoassay) is more
sensitive to adulterants than the required confirmatory drug test (GC/MS).
Currently, the GC/MS assays for marijuana metabolite (THCA) and opiates appear
to be affected by adulterants more than GC/MS assays for other drugs.
When a laboratory is unable to obtain a valid drug
test result or when drug or specimen validity tests indicate a possible
unidentified adulterant, the laboratory reports the specimen to the MRO as
"invalid result" (see Interpretation and Result Verification section below).
When an MRO receives an "invalid" specimen report, it is incumbent upon him/her
to discuss with the laboratory whether additional tests should be performed by
the laboratory or by another certified laboratory. It may be possible to obtain
definitive drug test results for the specimen using a different drug test
method or to confirm adulteration using additional specimen validity tests. The
choice of the second laboratory and/or additional tests will be dependent on
the suspect adulterant and the validated characteristics of the different drug
tests. Laboratory staff should be knowledgeable of their tests' validated
characteristics including effects of known interfering substances, and be able
to recommend whether additional testing is worthwhile.
HHS allows certified laboratories to test for any
adulterant. It is not possible to provide specific program guidance for all
substances that may be used as adulterants; however, HHS has included specific
requirements in the Guidelines for pH analysis and for the analysis of known
adulterants listed below:
pH of human urine is usually near neutral (pH
7), although some biomedical conditions affect urine pH. HHS set the program
cutoffs for pH based on a physiological range of approximately 4.5 to 9.
Specimens with pH results outside this range are reported as invalid. An
extremely low pH (i.e., less than 3) or an extremely high pH (i.e., at or above
11) is evidence of an adulterated specimen.
Nitrite is an oxidizing agent that has been
identified in various commercial adulterant products. Nitrite (NO2)
is produced by reduction of nitrate (NO3). Nitrite in high
concentrations is toxic to humans especially infants, causing methemoglobinemia
by oxidizing the iron in hemoglobin. Nitrate and, to a lesser extent, nitrite
are present in the environment. Nitrite may be present in human urine from the
following sources:
-
Food: Sodium nitrite is used as part of the curing
process for meat (e.g., ham, wieners). Nitrates are present in vegetables
(e.g., celery, spinach, beets, radishes, cabbage).
-
Drinking water: Water sources may become contaminated
with nitrate and nitrite due to run-off from farms using nitrogen fertilizers,
from septic systems, and from livestock feedlots. The levels of nitrate and
nitrite in public drinking water supplies are monitored because of the
potential health threat to infants under six months of age.
-
Occupational exposure: Workers in explosives and
pharmaceuticals manufacturing may be exposed to nitrates.
-
Medications: Organic nitrate and nitro compound drugs
(e.g., used for angina, congestive heart failure, ulcers) metabolize to
inorganic nitrite ion. Inorganic nitrite/nitrate salts have limited medical
uses (e.g., used for cyanide poisoning).
-
Endogenous production: The enzyme nitric oxide
synthase (NOS) catalyzes the endogenous formation of nitric oxide radical,
which oxidizes to nitrite and nitrate. This may result in normal human urine
containing a small amount of nitrate with an extremely small ratio of nitrite.
-
Pathological conditions: Some infectious and
inflammatory conditions (e.g., sepsis, asthma, rheumatoid arthritis,
tuberculosis, inflammatory bowel disease, Alzheimer's disease, multiple
sclerosis) induce another enzyme (i.e., inducible NOS) that catalyzes the
formation of nitric oxide radical.
-
Medical treatments: Some medical treatments (e.g.,
Interleukin-2 in cancer treatment) can induce NOS and result in nitrite in the
urine.
-
Urinary tract infections: Some urinary tract
infections are caused by bacteria that, if present in large numbers, may reduce
nitrate to nitrite by microbial action.
Because low levels of nitrite may be present in human
urine due to the reasons listed above, HHS set a cutoff level of 500 mcg/mL for
adulteration and 200 mcg/mL for invalid results. These concentrations are well
above levels seen in human urine. Therefore, these reasons do not
explain a nitrite adulterated result.
Chromium (VI) is a strong oxidizing agent that has been identified in
various commercial adulterant products. The most common forms of the element
chromium are chromium (0), chromium (III), and chromium (VI). All have
industrial uses. Both chromium (III) and chromium (VI) are used for chrome
plating, dyes and pigments, leather tanning, and wood preserving. Chromium
(III) is an essential nutrient and is always present in humans. Chromium (VI)
is toxic and has been shown to be a human carcinogen. The presence of chromium
(VI) in a urine specimen is indicative of adulteration. HHS set an initial test
cutoff level of 50 mcg/mL for chromium (VI).
Surfactants, including ordinary
detergents, have been used to adulterate urine specimens. Surfactants have a
particular molecular structure made up of a hydrophilic and a hydrophobic
component. They greatly reduce the surface tension of water when used in very
low concentrations. Foaming agents, emulsifiers, and dispersants are
surfactants that suspend an immiscible liquid or a solid, respectively, in
water or some other liquid. Surfactants tend to clump together when in
solution, forming a laminar surface between the fluid and air with their
hydrophobic components along the surface and their hydrophilic components in
the fluid. Often surfactants will form "bubbles" (micelles) within the fluid: a
small sphere of hydrophilic "heads" surrounding a pocket containing the
hydrophobic "tails." They can also form bubbles in air (i.e., two nested
spheres of surfactant with a thin layer of water between them, surrounding a
pocket of air) and can form "antibubbles" in fluid (i.e., a layer of air
surrounding a pocket of water).
Halogens are the four elements fluorine,
chlorine, bromine, and iodine. Halogen compounds have been used as adulterants.
The term "halogen" (from the Greek hals, "salt," and gennan, "to form or
generate") was given to these elements because they are salt formers. None of
the halogens can be found in nature in their elemental form. They are found as
salts of the halide ions (F-, Cl-, Br-, and I-). Fluoride ions are found in
minerals. Chloride ions are found in rock salt (NaCl), the oceans, and in lakes
that have a high salt content. Both bromide and iodide ions are found at low
concentrations in the oceans, as well as in brine wells. The assays used by
certified laboratories identify halogen compounds that act as oxidants. These
do not include the halogen salts that may be present in a urine specimen. The
presence of an oxidative halogen in a urine specimen is evidence of
adulteration.
Glutaraldehyde is a clear, colorless
liquid with a distinctive pungent odor sometimes compared to rotten apples. One
of the first effective commercial adulterants was found to contain
glutaraldehyde. Glutaraldehyde is used as a sterilizing agent and disinfectant,
leather tanning agent, tissue fixative, embalming fluid, resin or dye
intermediate, and cross-linking agent. It is also used in X-ray film
processing, in the preparation of dental materials, and surgical grafts.
Glutaraldehyde reacts quickly with body tissues and is rapidly excreted. The
most common effect of overexposure to glutaraldehyde is irritation of the eyes,
nose, throat, and skin. It can also cause asthma and allergic reactions of the
skin. Glutaraldehyde at any detectable level in a urine specimen is evidence of
adulteration.
Pyridinium chlorochromate is a strong
oxidizing agent that has been identified in some commercial adulterants. This
compound is confirmed by urine drug testing laboratories using a confirmatory
test for pyridine. Pyridine is a colorless liquid that can be prepared from
crude coal tar or from other chemicals. Pyridine formed from the breakdown of
natural materials results in very low levels in air, water, and food. It is
used as a solvent, and also used in the preparation of medicines, vitamins,
food flavorings, paints, dyes, rubber products, adhesives, insecticides, and
herbicides. There is little information on the health effects of pyridine,
although some animal studies and human case reports have noted liver damage
from exposure to pyridine. Human exposure may occur by various means (e.g.,
inhalation or dermal exposure of workers in industries that make or use
pyridine, inhalation of pyridine released into air from burning cigarettes or
hot coffee, exposure to air or water contaminated from hazardous waste sites or
landfills). The U.S. Food and Drug Administration (FDA) allows its use as a
flavoring agent in food preparation. Pyridine at any detectable level in a
urine specimen is evidence of adulteration.
D. Dilution/Substitution
A donor may attempt to decrease the concentration of
drugs or drug metabolites that may be present in his or her urine by dilution.
Deliberate dilution may occur in vivo by consuming large volumes of liquid,
often in conjunction with a diuretic, or in vitro by adding water or another
liquid to the specimen. Donors also have been known to substitute urine
specimens with drug-free urine or other liquid during specimen collection. Due
to donor privacy considerations, collections for federally regulated drug
testing programs are routinely unobserved. Therefore, dilution and substitution
may be undetected by collectors and be viable methods for defeating drug tests.
There are products on the market today purporting to "cleanse" the urine prior
to a drug test; many of which are diuretics. There are also products designed
specifically for urine specimen substitution, including drug-free urine,
additives, and containers/devices to aid concealment. Many such devices have
heating mechanisms to bring the substituted specimen's temperature within the
range set by HHS to determine specimen validity at the time of collection
(i.e., 32º to 38ºC/90º to 100ºF). Some include prosthetic devices to deceive
the observer during a direct observed collection.
To identify diluted and substituted specimens, HHS
developed criteria for evaluating specimens for the following human urine
characteristics:
Creatinine is a protein produced by
muscle and cleared from the body by the kidneys. It is a normal constituent in
urine. Normal human urine creatinine concentrations are greater than 20 mg/dL.
Abnormal levels of urine creatinine may result from excessive fluid intake,
glomerulonephritis, pyelonephritis, reduced renal blood flow, renal failure,
myasthenia gravis, or a high meat diet.
Specific gravity is a measure of the
density of a substance compared to the density of water. For urine, the
specific gravity is a measure of the concentration of particles in the urine.
Normal values for the specific gravity of human urine range from approximately
1.0020 to approximately 1.0200. Decreased urine specific gravity values may
indicate excessive fluid intake, renal failure, glomerulonephritis,
pyelonephritis, or diabetes insipidus. Increased urine specific gravity values
may result from dehydration, diarrhea, excessive sweating, glucosuria, heart
failure, proteinuria, renal arterial stenosis, vomiting, and water restriction.
Laboratories are required to test the creatinine in all regulated specimens,
and to test specific gravity for specimens with creatinine less than 20 mg/dL.
There are established program cutoffs for identifying invalid, dilute, or
substituted specimens based on the paired creatinine and specific gravity test
results. Appendix A describes Laboratory Reporting Criteria from the HHS
Guidelines.
Chapter 4. The MRO Review and
Reporting Process
The MRO must review all non-negative test
results (i.e., positive, adulterated, substituted, invalid) and all negative and
dilute specimens before reporting the results to the Federal agency's
designated representative. Negative specimen results may be reviewed and
reported by staff under the direct, personal supervision of the MRO.
The MRO process consists of:
-
Administrative review of documents,
-
Interview with the donor (as required),
-
Handling retest requests (as required),
-
Result interpretation and verification, and
-
Reporting of results to the Federal agency's
designated representative.
No regulatory requirements exist requiring MROs to use
specific procedures to review drug tests; however, using a standard procedure
better ensures that the MRO review for each specimen is complete and thorough.
A simple checklist can be helpful in assuring consistency and completeness of
the process.
A. Administrative Review of
Documents
1. MRO Copy of the Federal CCF (Copy 2)
The collector is required to send the MRO Copy of the
Federal CCF (Copy 2) to the MRO within 24 hours or one business day after the
collection. If the MRO receives a laboratory test report for a specimen without
having received the MRO copy of the Federal CCF, the MRO must contact the
collector. If the MRO copy is not available, the MRO must obtain another
legible copy of the Federal CCF (e.g., collector or employer copy) that has
been signed by the donor and has the donor's name and telephone number(s).
The following items are verified for Copy 2 of the
Federal CCF:
a. The correct OMB-approved Federal CCF was used to
document the specimen collection.
b. The Federal CCF contains the specimen
identification number.
c. The testing laboratory is identified by one of the
following:
-
A specific laboratory name and address at the top of
the CCF,
-
A list of addresses with check boxes at the top of
the Federal CCF (the collector checks the box for the laboratory to which the
specimen will be delivered), or
-
A corporate name and telephone number at the top of
the Federal CCF and the specific laboratory address in the "Test Lab" line in
Step 5a.
d. The Federal CCF was properly completed:
-
Federal agency name and address,
-
MRO name, address, and telephone number,
-
Donor identification (e.g., SSN, employee
identification number),
-
Reason for the test,
-
Tests to be performed, and
-
Collection site information (i.e., address, telephone
number, and fax number)
-
The temperature of the specimen was or was not within
the required temperature range,
-
The collection was a split specimen or single
specimen collection,
-
No specimen was collected and why (if applicable),
-
A direct observed collection was performed and why
(if applicable), and
-
Comments on the "Remarks" line (as appropriate)
recording the collector's observations or explanatory comments concerning the
donor, the specimen, or collection events.
-
Collector's printed name,
-
Collector's signature,
-
Date and time of the collection, and
-
Specific name of the delivery service that was used
to transfer the specimen to the laboratory.
-
Donor's printed name,
-
Donor's signature,
-
Date signed,
-
Donor's daytime telephone number,
-
Donor's evening telephone number, and
-
Donor's date of birth.
2. Laboratory Report - Federal CCF (Copy 1) and/or
Computer-Generated Electronic Report
Certified laboratories report drug test results only
to the MRO. The laboratory and the MRO must have procedures in place to ensure
the confidentiality of the reports (i.e., hardcopy and electronic). The
laboratory may send drug test reports by:
-
Courier,
-
Mail,
-
Secure fax, and
-
Secure electronic transmission.
The following items are verified for the laboratory
report for a specimen:
a. The specimen identification number on the
laboratory copy of the Federal CCF (Copy 1) and/or on any other laboratory
report matches that on the MRO copy (Copy 2) for the identified donor.
b. The Federal CCF was properly completed:
-
Accessioner's printed name,
-
Accessioner's signature, and
-
Documentation of the bottle seal condition upon
receipt at the laboratory.
-
For a single or primary (Bottle A) specimen, Step 5a
contains:
-
Test results,
-
Certifying scientist's printed name,
-
Certifying scientist's signature,
-
Date of result certification,
-
Comments on the "Remarks" line (as appropriate):
-
Quantitative test results
-
Comments as required by HHS for specimens reported as
"adulterated," "rejected for testing," or "invalid result"
-
Observations or explanatory comments recorded by
laboratory staff concerning the specimen, and
-
Name and address of the testing laboratory (if not on
the top of Copy 1).
-
For a retest specimen, Step 5b contains:
-
Test results,
-
Certifying scientist's printed name,
-
Certifying scientist's signature,
-
Date of result certification,
-
Comments on the "Remarks" line (as appropriate):
-
Quantitative test results
-
Comments as required by HHS for specimens that failed
to reconfirm
-
Observations or explanatory comments recorded by
laboratory staff concerning the specimen, and
-
Name and address of the testing laboratory.
c. The laboratory has included a memorandum from the
collector to address any correctable flaws identified. See Section 3 below.
d. The computer-generated electronic report (if any)
contains the HHS-required information as follows:
-
Laboratory name and address,
-
Federal agency name,
-
MRO name,
-
Specimen identification number,
-
Donor identification from the Federal CCF (e.g., SSN,
employee ID number),
-
Collector name and telephone number,
-
Reason for test (if provided),
-
Date of collection,
-
Date received at laboratory,
-
Certifying scientist's name,
-
Date certifying scientist released the results,
-
Test results, and
-
Additional comments concerning the specimen's testing
and processing, as listed in the "Remarks" line of the Federal CCF.
e. The information on the computer-generated
electronic report (if any) is consistent with that on the laboratory copy of
the Federal CCF (Copy 1).
3. Federal CCF or Specimen Errors
A laboratory or an MRO may identify errors made on a
Federal CCF, or a laboratory may identify a problem with a specimen during
processing. The various types of errors are outlined below:
a. Uncorrectable errors that result in specimen
rejection by the laboratory and test cancellation by the MRO:
-
Specimen ID number on the Federal CCF and bottle
label/seal do not match or the number is missing on either the Federal CCF or
the specimen bottle label/seal,
-
Specimen bottle label/seal is missing or broken on
the specimen from a single specimen collection or on a primary specimen (Bottle
A) of a split specimen collection and the split specimen (Bottle B) cannot be
redesignated as the primary specimen,
-
The collector's signature and printed name are
omitted from the CCF, or
-
There is insufficient specimen volume for testing.
b. Correctable errors that result in specimen
rejection and/or cancellation unless corrected by a memorandum for the record
(MFR) from the collector:
-
The collector failed to sign the CCF (but the printed
name is present), or
-
The collector used a non-Federal form or an expired
version of the Federal CCF.
c. Federal CCF omissions and discrepancies that are
considered insignificant when they are infrequent (i.e., when a collector does
not make the error more than once a month). Examples include, but are not
limited to:
-
No collection date/time,
-
No courier entry,
-
No specific delivery service name, or
-
Donor name included on the laboratory copy of the
CCF.
d. Administrative errors made by laboratory staff that
are judged by the MRO to have a significant impact on the forensic
defensibility of the results unless corrected by an MFR. Examples include, but
are not limited to:
-
No accessioner signature on the CCF,
-
No documentation of bottle seal condition on the CCF,
or
-
No certifying scientist signature on the CCF.
4. Federal CCF Remarks
Collectors are required to include comments on the
"Remarks" line in Step 4 (the collector's section) of the Federal CCF to
document any unusual donor behavior or incidents occurring during the
collection. Laboratory staff are required to include comments on the "Remarks"
line in Step 5a of the Federal CCF to document any issues concerning the
specimen (e.g., redesignation of the A and B Bottles), as well as explanatory
reporting comments required by the program (e.g., the basis for reporting a
specimen as adulterated, the basis for reporting an "invalid result," reason
for rejection).
The MRO evaluates whether information provided on the
Federal CCF "Remarks" lines have a significant impact on the forensic
defensibility of the drug test results. If the MRO believes the forensic
defensibility of the results is affected, he or she either attempts to obtain
an MFR or cancels the test.
5. Actions Based on Administrative Review
When an uncorrectable error is identified (see
Item 3.a above):
a. If the laboratory identifies the error, the
laboratory rejects the specimen for testing and reports the specimen as
rejected to the MRO. The reason for rejection is included on the laboratory
report(s) to the MRO.
b. If the MRO receives a rejected for testing report
or identifies an uncorrectable error during review, the MRO cancels the test.
c. The MRO reports the cancellation and the reason to
the Federal agency, which then determines whether or not to immediately collect
another urine specimen from the donor.
When a correctable documentation/specimen error (see
Item 3.b above) by the collector is identified by either the laboratory or the
MRO, the collector is notified to provide an MFR to address the error:
-
The laboratory includes a copy of the MFR with the
report to the MRO.
-
The MRO reports the verified result (see Section D
below) to the Federal agency and maintains the MFR in the files for the
specimen.
b. If the collector does not provide an MFR:
-
The laboratory holds the specimen for a minimum of 5
business days after requesting the MFR, then reports the specimen as rejected
and discards the specimen. The reason for rejection is included on the
laboratory report(s) to the MRO.
-
The MRO cancels the test and notifies the Federal
agency of the cancelled test and the reason for cancellation.
When the laboratory and/or MRO document frequent
insignificant errors by an individual collector (see Item 3.c):
a. The MRO notifies the collector/collection site of
the errors.
b. The collector/collection site takes appropriate
corrective actions (e.g., revises procedures, retrains the individual and other
collectors at the collection site) and submits a copy of documentation of the
action(s) to the MRO.
c. The MRO maintains the documentation of error
notification and corrective action response in his or her records.
B. Donor Interview
The MRO must contact the donor and interview the donor
when the donor's specimen is reported by the laboratory as non-negative (i.e.,
positive, adulterated, substituted, invalid).
The MRO must attempt contact as soon as possible after
receiving the report (usually within 24 hours). The MRO copy of the Federal CCF
will contain daytime and evening telephone numbers for the donor.
The MRO should establish guidelines as to what
constitutes a reasonable effort to contact a donor. All attempts made to contact
the donor must be documented.
If the MRO, after making all reasonable efforts, has
been unable to contact the donor within 14 days after the date on which
the MRO received the test result from the laboratory:
1. The MRO must inform the Federal agency of his or
her inability to contact the donor.
a. The MRO must not reveal the test result or any
information about the drug test.
b. The Federal agency must:
-
Confidentially direct the donor to contact the MRO
within 5 days, and
-
Inform the MRO once the donor has been directed to
contact the MRO or if the Federal agency was unable to contact the donor.
2. The MRO may verify a test result without having
communicated directly with the donor (i.e., a non-contact determination) for
the following reasons:
a. The donor expressly declines the opportunity to
discuss the test result, or
b. The Federal agency has contacted the donor and
instructed the donor to contact the MRO, but the donor has not contacted the
MRO within 5 days after being contacted by the Federal agency.
The Interview Process
1. Request the donor to provide information that will
verify the donor's identity (e.g., employee identification number, SSN) to
ensure that it agrees with the information documented on the Federal CCF. (This
step may be done by staff under the MRO's supervision; however, the MRO must
personally perform all other steps of the interview process as listed below).
2. Inform the donor, prior to obtaining any
information, that confidential medical information provided during the review
process may be disclosed to the Federal agency.
3. Inform the donor of the laboratory reported test
result(s).
4. Take action based on the donor's response:
a. If the donor admits use of an illegal drug
consistent with the test results or admits that he or she tampered with the
specimen, advise the donor that the test result will be reported to the Federal
agency.
b. If the donor does not admit use of an illegal drug
or specimen tampering, ask the donor if there is any possible medical
explanation for the test result:
-
If the donor provides a possible medical explanation
(e.g., claims that a positive result was due to a legally prescribed medication
or that the drug use was associated with a valid medical procedure), require
the donor to provide appropriate supporting documentation within a specified
time.
-
If the donor has no valid medical explanation for the
result, advise the donor that the test result will be reported to the Federal
agency.
5. For positive, substituted, or adulterated results:
Inform the donor that he or she may have the specimen retested at a second
certified laboratory. The retest request must be made within 72 hours of the
interview with the MRO. (Note that donors are not allowed to request retesting
of specimens reported as invalid.)
a. If the donor requests a retest, use the procedures
described in Section C (Handling Retest Requests) to direct the laboratory to
send the retest specimen to another certified laboratory for confirmatory
testing.
b. If the donor does not request a retest, document
that the donor was informed of and declined the opportunity for a retest.
C. Handling Retest Requests
Note: Donors are not allowed to request retesting of
specimens reported as invalid.
The following are rules for handling retest requests
for positive, adulterated, or substituted specimens:
1. The donor has 72 hours from the time the MRO
notified the donor that his or her specimen was reported positive, adulterated,
or substituted to request the retest.
2. The MRO must request the retest of a single
specimen or the test of the split (Bottle B) specimen in writing (i.e., a
memorandum or letter format). The written request may be mailed, faxed, or
electronically sent to the laboratory where the primary specimen was tested and
must contain the following information:
-
MRO name and address (use MRO letterhead),
-
Laboratory name and address (i.e., Laboratory A)
where original analysis was performed,
-
Specimen ID Number on the Federal CCF,
-
Laboratory Accession Number (i.e., the number
assigned by Laboratory A to the specimen when it was accessioned),
-
Request for confirmatory retest for the
drug/metabolite, adulterant, or substitution reported by Laboratory A, and
-
Name and address of the HHS-certified laboratory
(i.e., Laboratory B) selected to retest the specimen (i.e., aliquot of a single
specimen or the split (Bottle B) specimen).
3. Laboratory B may be selected by the MRO, the
Federal agency, or the donor. In most instances where retesting is requested,
the first laboratory will have blanket purchase agreements with 2 or 3 other
certified laboratories to make the billing and payment process easier.
4. If the specimen cannot be tested by a second
laboratory (e.g., insufficient volume, lost in transit, Bottle B not available,
no other certified laboratory tests for the specific adulterant), the MRO shall
direct the Federal agency to immediately collect another specimen using a direct
observed collection procedure.
-
If the test is cancelled because no other certified
laboratory tests for the specific adulterant, the MRO notifies the appropriate
regulatory office.
5. The second HHS-certified laboratory reports retest
results directly to the MRO using Copy 1 of the Federal CCF.
6. The MRO reports the result to the Federal agency
and the donor.
D. Interpretation and Result
Verification
The Drug Information section above provides
information on the drugs specified in the HHS Mandatory Guidelines for testing
in Federal agency workplace programs, including the current CSA schedules,
signs/symptoms of abuse, and metabolism information.
The MRO interprets drug test results based on:
-
The laboratory results,
-
The donor's explanation and supporting documentation,
and
-
The MRO's medical assessment of the donor's behavior
and physical symptoms during the donor interview.
The MRO must report only verified results to the
Federal agency. The MRO must not inform the Federal agency when a positive,
adulterated, or substituted result was verified as negative.
Table 5 describes MRO actions to be taken for
primary specimen results.
Table 6 describes MRO actions to be taken for
retest specimen results.
Laboratory Results
Laboratory staff are available to answer MRO questions
concerning reported drug test results. However, laboratories are strictly
prohibited from providing any information about a specimen's result prior to
completion of testing and are prohibited from providing any drug test results
over the telephone.
The Mandatory Guidelines provide specific reporting
criteria for certified laboratories to report Federal agency specimen results.
These criteria are described in Appendix A. The laboratory must report
all non-negative results for a specimen, as supported by data.
After receiving a drug test report, the MRO should
contact the laboratory whenever additional information is needed. For example,
the MRO may wish to clarify the laboratory's administrative and analytical
procedures, or obtain quantitative results or other information that could be
useful in evaluating the validity of a donor's explanation. General information
may be given over the telephone. Requests for information about a specific
specimen (e.g., quantitative results) must be made by the MRO in writing. The
written request may be mailed, faxed, or electronically sent to the laboratory.
The term "invalid result" is used when a
scientifically supportable negative test result cannot be established for a
specimen due to an unidentified adulterant, an interfering substance, an
abnormal physical characteristic, or an endogenous substance at an abnormal
concentration (see criteria in Appendix A).
When the MRO receives a report of "invalid result,"
the MRO must discuss the result with the laboratory to determine if additional
testing by another certified laboratory could provide a definitive result
(i.e., negative, positive, or adulterated). Specimens reported as invalid based
on creatinine and specific gravity results or on pH are exceptions to this rule.
The MRO is not required to contact the laboratory when a specimen is reported
as invalid for these reasons. It is unlikely that testing by another certified
laboratory would provide different results.
Donor Explanation
As noted previously, one of the purposes for a donor
interview is to allow a donor the opportunity to provide an alternative
explanation for a non-negative drug test result. For the explanation to be
accepted, the donor must provide acceptable supporting documentation to the
MRO. If the alternative explanation for a positive, adulterated, or substituted
result is acceptable and supported by documentation as outlined below, the MRO
must verify the result as negative.
Prescriptions
If the donor claims to have taken a prescribed
medicine that contains either the drug reported positive or a substance that
can metabolize to that drug, the donor must provide one of the following:
-
A copy of the prescription,
-
The medicine container with the appropriately labeled
prescription (or the label from the container), or
-
A copy of the medical record documenting the valid
medical use of the drug during the time of the drug test.
The MRO may contact the prescribing physician or the
pharmacist who filled the prescription to verify the information provided by
the donor.
If the donor has been taking a prescription medication
that contains a drug with a high potential for abuse for a long time, there
must be appropriate justification for the long term use. The MRO must contact
the prescribing physician to express concern that the continued use of the
medication may present a significant safety problem for the donor while on the
medication.
State initiatives and laws which make available to an
individual a variety of illicit drugs by a physician's prescription or
recommendation do not make the use of these illicit drugs permissible under the
Federal Drug-Free Workplace Program. These State initiatives and laws are
inconsistent with Federal law and put the safety, health, and security of
Federal workers and the American public at risk.
The use of any substance included in Schedule I of the
Controlled Substance Act, whether for non-medical or ostensible medical
purposes, is considered a violation of Federal law and the Federal Drug-Free
Workplace Program. These drugs have no currently accepted medical use in
treatment in the United States and their use is inconsistent with the
performance of safety-sensitive, health-sensitive, and security-sensitive
positions, and with drug-free workplace programs.
The MRO must not accept a prescription or the verbal
or written recommendation of a physician for a Schedule I substance as a valid
medical explanation for the presence of a Schedule I drug or metabolite in a
Federal employee/applicant specimen.
Interpretation of Results
Dilute Specimens
A laboratory may report a specimen as dilute in conjunction with a positive or
negative drug test. A donor may produce urine that meets the program criteria
for dilution under some conditions including:
-
Working in hot weather conditions drinking large
amounts of fluid,
-
Taking a diuretic, or
-
Drinking fluids immediately before providing the
specimen.
The MRO actions to be taken in response to a dilute
specimen report depend on whether the drug test result is positive or negative.
These MRO actions are shown in Table 5.
Substituted Specimens
The HHS criteria for identifying substituted specimens
are based on the physiological ranges for creatinine concentration and specific
gravity value of normal human urine. If the donor denies substituting the
specimen, he or she is given the opportunity to prove the ability to produce
urine that meets substitution criteria as described below.
1. If the donor claims to have consumed a large
quantity of fluids prior to providing the urine specimen:
a. The MRO requests the Federal agency to have the
donor provide another specimen collected using a direct observed collection
procedure and have the collector document that the donor drank a similar
quantity of fluids prior to providing the specimen.
b. If the creatinine and specific gravity results for
the second specimen are similar to the results for the first specimen, this is
considered a legitimate explanation for the substituted result.
2. If the donor claims to have a pre-existing,
documented medical condition that causes the donor's urine to meet both the
creatinine and specific gravity criteria for a substituted specimen, the MRO
requests the donor to provide a copy of the medical record to support that
claim.
3. If the donor claims to have personal
characteristics (e.g., race, gender, weight, diet, working conditions) such
that his or her urine normally satisfies the substitution criteria:
a. The MRO requests the donor to demonstrate that he
or she can normally produce a substituted specimen.
b. The demonstration must provide a reasonable basis
to conclude that the donor's personal characteristics are a legitimate medical
explanation.
Adulterated Specimens
The MRO is required to contact the donor and give the
donor an opportunity to explain the adulterated result and to demonstrate that
the presence of the adulterant occurred through normal physiological means.
However, the program criteria for adulteration definitively prove adulteration.
There is no valid medical explanation for a urine specimen to meet the criteria
for an adulterated result under the HHS Mandatory Guidelines.
Amphetamines
Depending on the amphetamines confirmation method
(e.g., derivatization procedure, instrument parameters) used by a laboratory,
it is possible for some structurally similar compounds (i.e., sympathomimetic
amines) to be converted to methamphetamine during GC/MS analysis. HHS
instituted the following assay validation and reporting requirements that
prevent the possibility of false positive methamphetamine results due to this
conversion:
1. Laboratories are required to quantitate at least
200 ng/mL amphetamine in a specimen in order to report a positive
methamphetamine result. As described previously, methamphetamine metabolizes to
amphetamine. This occurs quickly, via a simple demethylation reaction. Because
the sympathomimetic amines are not converted to amphetamine, the presence of
amphetamine is supporting evidence for methamphetamine use.
2. Certified laboratories are required to validate all
assays prior to use with Federal agency specimens. For amphetamines
confirmatory assays, each laboratory must document the assay's ability to
identify and accurately quantitate methamphetamine and amphetamine in the
presence of high levels of sympathomimetic amines and also demonstrate that
these compounds are not misidentified as methamphetamine or amphetamine (i.e.,
by analyzing samples containing sympathomimetic amines without methamphetamine
or amphetamine). These experiments must be performed on at least an annual
basis, to verify the assay's continued performance.
Enantiomers
Most immunoassays used as the initial test in Federal workplace drug testing
programs are focused on d-methamphetamine. However, the l-methamphetamine
enantiomer and amphetamine enantiomers cross-react with the immunoassay
reagents. Amphetamines GC/MS assays identify both amphetamine and
methamphetamine and do not distinguish between enantiomers. Therefore, there is
a possibility that a laboratory positive result could be reported for
l-methamphetamine and/or l-amphetamine.
Laboratories may employ a chiral GC/MS assay that
distinguishes between the d- and l- enantiomers and determines the relative
percentages of each. HHS does not require each certified laboratory to have
this capability. Upon written request of the MRO, the laboratory may perform
the test or send a specimen to another certified laboratory for d- and l-
enantiomer testing.
When the MRO receives a methamphetamine positive
result from a laboratory, he or she may order enantiomer testing to aid in
result interpretation, as described below:
1. Prescription Drug Products. There are prescriptions
that contain amphetamine or methamphetamine. Enantiomer analysis may be used to
verify that a positive methamphetamine result was due to use of a legal drug.
For example, Selegiline is a brain monoamine oxidase inhibitor used in the
adjunctive treatment of Parkinson's disease and for depression. Selegiline is
metabolized to l-methamphetamine and l-amphetamine. A d- and l- isomer
differentiation will reveal the presence of only l-methamphetamine and
l-amphetamine after the ingestion of Selegiline.
2. Non-Prescription Drug Products. Some
non-prescription products contain sympathomimetic amines which can cause a
positive result on an initial immunoassay test. The confirmatory GC/MS test is
specific for methamphetamine and amphetamine. Specimens containing
sympathomimetic amines will not be reported positive by the laboratory after
conducting the confirmatory test. The Vicks Inhaler® is the only
over-the-counter drug that contains l-methamphetamine. Enantiomer analysis may
be used to verify that a positive methamphetamine result was due to its use.
There may be a trace amount of the d- isomer present because a very slight
amount of d-methamphetamine may be present as a contaminant in the Vicks
Inhaler® and a contaminant of the analytical procedure. If there is greater
than 80% l-methamphetamine, the results are considered to be consistent with
Vicks Inhaler® use. If there is more than 20% d-methamphetamine present, the
results indicate the use of some source other than the inhaler and the result
is verified as positive. This is a very conservative interpretation.
Cocaine
There are no prescription medications that contain
cocaine. However, the medical community uses TAC (tetracaine, adrenalin,
cocaine) as a topical preparation prior to various surgical procedures and may
use cocaine by itself as a topical vasoconstrictive anesthetic for various ear,
nose, throat, and bronchoscopy procedures. If cocaine is used, the licensed
physician performing the procedure would document its use in the donor's
medical record. The medical use must have occurred within 2 to 3 days prior to
when the urine specimen was collected. Use at an earlier time will not cause a
positive urine test.
Topical Anesthetics
Cocaine is structurally unique and does not resemble any of the other topical
anesthetics, such as Novocain®, Xylocaine®(lidocaine), benzocaine, etc.
Although these compounds have analgesic properties, there is no structural
similarity to cocaine or its metabolite (benzoylecgonine). Specimens containing
these substances will not be reported positive by the laboratory for
benzoylecgonine.
Passive Inhalation of Crack Cocaine
Comprehensive scientific studies have demonstrated
that individuals passively exposed to "crack" smoke do not produce a urine
positive for cocaine using the HHS cutoffs for initial and confirmatory
testing.
When a donor claims that his or her positive
benzoylecgonine test was due to passive inhalation, the MRO should allow the
donor to describe the circumstances pertaining to how and when the passive
exposure occurred. Passive inhalation is not an acceptable alternative
explanation for the presence of benzoylecgonine in the donor's urine.
Coca Leaf Tea
In the early 1980s, health food stores sold a tea under the trade name "Health
Inca Tea." It was discovered that this tea contained decocanized coca leaves
with detectable amounts of cocaine present and the U. S. Food and Drug
Administration banned the importation of this tea into the United States.
Therefore, any tea sold using the name "Health Inca Tea" should not contain any
cocaine.
When a donor claims that his or her positive
benzoylecgonine test was due to drinking a beverage with coca leaves as an
ingredient, the MRO should allow the donor to explain where and when the tea
was purchased. Drinking "Health Inca Tea" or other beverage purporting to
contain coca leaves is not an acceptable alternative explanation for the
presence of benzoylecgonine in the donor's urine.
Marijuana
There has been much discussion in the political and
medical fields over the years concerning the benefits of medicinal marijuana.
At this time, marijuana remains a Schedule 1 drug and marijuana use is not an
acceptable medical explanation for a positive drug test result in the Federal
agency drug testing program. A prescription or written recommendation from a
licensed physician or medical professional does not exempt the donor from this
rule. If the donor admits the use of medical marijuana, the MRO verifies the
result as positive.
Prescription THC
Dronabinol is chemically synthesized delta-9- tetrahydrocannabinol (THC®). It
is available under the trade name Marinol® in 2.5, 5, or 10 mg soft gelatin
capsules for oral administration. Marinol® may be used for stimulating appetite
and preventing weight loss in patients with a confirmed diagnosis of AIDS and
treating nausea and vomiting associated with cancer chemotherapy. Additionally,
a few individuals have been permitted by a court order to use THC® for the
management of glaucoma. Patients that are prescribed Marinol® should be warned
not to drive, operate complex machinery, or engage in hazardous activity.
There are no other prescription or over-the-counter
medications that contain cannabinoids or any other substances that might be
identified as or metabolized to THC® or its acid metabolite.
When a donor claims to have a prescription for Dronabinol or a court order
allowing the use of THC®, the MRO should allow the donor the opportunity to
provide the supporting documentation.
Passive Inhalation or Unknowing Ingestion of Marijuana
Passive inhalation and unknowing ingestion (i.e., an
inadvertent exposure to marijuana) are frequent excuses for positive urine
tests. Passive inhalation of marijuana smoke does occur and can result in
detectable levels of THC® and its metabolites in urine. Clinical studies have
shown, however, that it is highly unlikely that a non-smoking individual could
unknowingly inhale sufficient smoke by passive inhalation to result in a high
enough drug concentration in urine for detection at the cutoff levels used in
the Federal agency program. Similarly, it is extremely difficult to achieve
detectable levels through unknowing ingestion of plant material (e.g., leaves,
stems) or marijuana in food products. Studies have also shown that any
measurable peak concentration in urine occurs within several hours after the
exposure.
When a donor claims that his or her positive THCA test
was due to passive inhalation or unknowing ingestion, the MRO should allow the
donor to describe the circumstances pertaining to how and when the
exposure/ingestion occurred. Generally, the circumstances will not approximate
what would be needed to explain the presence of THC® in the donor's urine.
Hemp Products
The Drug Enforcement Agency (DEA) issued its final rule clarifying control of
natural and synthetic tetrahydrocannabinol (THC®) effective April 21, 2003 (21
CFR Part 1308). The rule states that it is illegal for anyone to manufacture,
distribute or market products used, or intended for use, for human consumption
that contain any amount of THC®. Personal care products (e.g., shampoos,
lotions) are not considered to fall in this category, because they are not
intended for human consumption and studies have shown that use of these
products does not cause urine specimens to test positive for THC® under the
Federal Guidelines. Other "non-consumable" hemp items (e.g., clothing,
industrial solvents, and animal feed mixtures) are considered non-controlled
substances and are not subject to any of the CSA requirements regardless of
their THC® content.
When a donor claims that his or her positive THCA test
was due to ingestion or use of a legal hemp product, the MRO should allow the
donor to explain where and when the product was purchased and used. Generally,
the circumstances will not approximate what would be needed to explain the
presence of THCA in the donor's urine.
Opiates
The opiate drug class poses some unique challenges
with regard to interpreting a positive test result. A positive result for
codeine or morphine may be from the following:
-
A drug product that contains codeine or morphine (see
Table 3 for some examples), or
-
Poppy seeds.
Eating a normal dietary amount of poppy seeds can
cause a urine specimen to test positive for morphine and codeine. The
concentration of morphine can be substantial, with usually very low
concentrations or no detectable codeine. In many instances, a donor will not
know that poppy seeds can cause a positive test or realize that he or she had
eaten poppy seeds at the time the urine was collected.
HHS included additional criteria in the Mandatory
Guidelines to distinguish between specimens testing positive due to opiates
abuse and specimens testing positive due to legitimate medical use or food
sources. The criteria are as follow:
-
When a laboratory reports a specimen as positive for
codeine and/or morphine and the quantitative results for both codeine and
morphine are less than 15,000 ng/mL:
-
If there is clinical evidence of illegal use of any
opium, opiate, or opium derivative (e.g., morphine/codeine) listed in CSA
Schedule I or II, the MRO verifies the result as positive.
-
If there is no clinical evidence of illegal use, the
MRO verifies the result as negative.
-
When a laboratory reports a specimen as positive for
codeine and/or morphine and the codeine and/or morphine result is greater than
or equal to 15,000 ng/mL:
-
If the donor does not present a legitimate medical
explanation for the presence of morphine or codeine (e.g., a valid
prescription), the MRO verifies the result as positive. Consumption of food
products is not a legitimate medical explanation for the donor having morphine
or codeine at or above this concentration.
-
If the donor presents a legitimate medical
explanation for the presence of morphine or codeine (e.g., a valid
prescription), the MRO verifies the result as negative.
-
When a laboratory reports a specimen as positive for
the heroin metabolite (6-acetylmorphine), this is proof of heroin use. The MRO
verifies the result as positive.
The MRO relies on his or her medical knowledge to
identify signs and symptoms of abuse during the donor interview. Clinical
evidence of illegal use may include, but is not limited to:
-
A donor's admission that he or she took a
prescription medication containing codeine or morphine that was prescribed to
another individual,
-
Recent needle marks, or
-
Behavioral and physiological signs of acute opiate
intoxication or withdrawal.
An MRO may have a blanket written request on file at
the laboratory to routinely receive the quantitative values associated with
positive codeine and morphine results. The MRO also may request quantitative
information on the presence of codeine below the cutoff for specimens that have
been reported positive for morphine only. This information may be helpful to
the MRO in assessing the medical explanation provided by the donor.
Other Narcotic Analgesics
Occasionally, a donor will reveal information regarding the use of a narcotic
analgesic (that does not contain codeine or morphine) believing that this
medication was the reason for the positive codeine or morphine. Assuming that
it was a legally prescribed medication, this confidential medical information
cannot be provided to the Federal agency and is not an explanation for the
positive codeine or morphine. Since the use of a narcotic analgesic may have a
possible effect on the ability of the donor to perform a specific task (e.g.,
driving a vehicle), it may be appropriate to discuss the use of the medication
with the prescribing physician. Additional guidance on reporting such
information is provided in Section F below and in Section C of Chapter 6.
Phencyclidine
A positive phencyclidine (PCP) result is evidence of
illegal drug use. There are no prescription or over-the-counter medications
that contain PCP, there are no legal medical uses of PCP, and there are no
other substances that can be misidentified as PCP using GC/MS.
Retest Results
After a second certified laboratory tests an aliquot
of the single specimen or the split (Bottle B) specimen, the MRO must take
actions in response to the second laboratory's reported results as outlined in
Table 6.
If the second laboratory believes that the analyte
(i.e., drug, drug metabolite, adulterant) is present in the retest specimen,
but cannot reconfirm its presence, the laboratory must consult with the MRO to
decide whether to send the specimen (i.e., the remaining aliquot of a single
specimen or Bottle B of a split specimen) to a third certified laboratory for
additional confirmatory testing. (If there is an insufficient quantity of urine
remaining in the aliquot of the single specimen at the second laboratory, the
MRO may request the first laboratory to obtain another aliquot from the
original specimen bottle and send it to the third laboratory.) The third
laboratory should be selected such that it uses a confirmation method more
similar to that used by the first laboratory (i.e., the laboratory that
reported the non-negative result for the primary specimen).
E. Reporting
After the review and verification processes have been
completed, the MRO reports the final, verified result(s) for a specimen to a
Federal agency. Reporting instructions are detailed in Tables 5 and 6.
The MRO must send the report using one of the
following methods, in a manner designed to ensure confidentiality of the
information:
-
Secure fax,
-
Courier,
-
Mail, or
-
Secure electronic transmission.
The report may be:
-
A legible image or copy of the completed Copy 2 of
the Federal CCF, or
-
A separate letter or memorandum for each specimen
that contains the following:
-
Donor's name and SSN or employee ID number,
-
Specimen ID number from the Federal CCF,
-
Result for the test as indicated on the Federal CCF,
-
Relevant comments provided by the collector and/or
laboratory on the Federal CCF,
-
Relevant information from the MRO (e.g.,
documentation of attempts to contact the donor, a statement of the donor's
refusal to cooperate with the medical review process),
-
Information provided by the donor (especially at the
donor's request) to the report (Note: this must not include specific
confidential medical information),
-
MRO's printed name and signature, and
-
Date reported.
The MRO must not disclose any numerical values to the
Federal agency.
Confidentiality
The Mandatory Guidelines require the MRO to:
1. Report the final result of the drug test to a
Federal agency in a manner designed to ensure the confidentiality of the
information, and
2. Maintain the confidentiality of the information
received during the review process, including:
-
information related to the donor's medical condition,
-
medications,
-
medical diagnosis, and
-
medical history.
Despite this general requirement to maintain the
confidentiality of medical information, there are certain circumstances in
which the MRO may provide such information to other parties. In these
instances, prior to the medical interview the MRO must inform the donor that
disclosure of information learned as part of the medical review process may
occur if:
-
There is a significant safety hazard associated with
donor performing assigned duties,
-
Medical disqualification of the donor exists under
applicable regulations, or
-
The Federal agency's regulations specify requirements
for disclosure of such information under other circumstances.
When the MRO releases otherwise confidential
information due to such concerns, the MRO must attempt to release as little
specific information as possible and release such information only to parties
that clearly "need-to-know." Such parties include:
-
Physicians responsible for medical certification of
the donor,
-
Federal agency officials as required by regulation,
or
-
Designated Federal agency representatives.
Diagnoses or other specific details of medical
information do not need to be provided to non-medical personnel. For example,
Federal agency representatives may only need to be informed that a safety
hazard may exist and that the MRO will provide specific information to the
physician responsible for making medical qualification decisions regarding the
donor. In general, unless required by regulation or law, the MRO must only
discuss specific medical information with other physicians or qualified health
professionals.
Chapter 5. Documentation and
Recordkeeping
Accurate recordkeeping is essential in documenting all
aspects of the MRO review process. All MRO activities should be properly
documented, to provide a record that procedures used were consistent with the
Mandatory Guidelines. The MRO should maintain documentation of all
communications (written and oral) with:
-
Donors,
-
Federal agency representatives,
-
Laboratory personnel, and
-
Collectors.
Although the Mandatory Guidelines do not specify the
length of time that MROs must retain drug test records, it is recommended that
they be maintained for a minimum of two years from the date of collection, or
as otherwise provided by law or contract with the Federal agency.
Documentation for each specimen must be retained in
the donor files and normally includes such things as:
-
Documentation to support an alternative medical
explanation for a non-negative result (e.g., copies of prescriptions, labels
from prescription bottles, notes that a prescription was verified at a pharmacy
or by the treating physician),
-
Letters or notes received from an employee, relative,
or physician providing treatment, or
-
MRO actions regarding the test (e.g., attempts to
contact the donor, documentation of the donor interview, any checklists used by
the MRO and MRO staff for the record).
Some MROs may serve as primary care providers and
retain medical records related to that function. MRO records must be separated
from other medical and personnel records kept on an individual.
A donor has the right, upon written request, to
records relating to his or her drug test. In addition, information can be
requested by a subpoena or court order. If an MRO has any concern regarding the
release of information associated with drug testing results, the MRO may want
to obtain a legal opinion.
The maintenance of donor confidentiality is
particularly important with respect to confirmed non-negative drug test
results, and especially for those that may be verified by the MRO as negative
due to a valid medical explanation.
Chapter 6. Additional MRO
Responsibilities
A. Federal Agency Blind Samples
Federal agencies are required to have blind samples
submitted with donor specimens. Blind samples are helpful in determining if the
entire testing process (i.e., from the collector's submission of a specimen to
a laboratory until a result is reported to the MRO) satisfies all requirements.
To ensure that the blind samples purchased from
different sources are acceptable, Federal agencies must use only samples
certified by the sample suppliers. Samples must be certified:
1. To have the stated results as verified by the
program-required method(s) of analysis:
a. Negative (verified by immunoassay and GC/MS),
b. Drug positive (verified by immunoassay and GC/MS),
c. Adulterated (verified by initial and confirmatory
specimen validity testing methods as appropriate), and
d. Substituted (verified by confirmatory creatinine
and specific gravity tests).
2. To have acceptable performance demonstrated up to
the stated expiration date and documented by stability studies.
The blind samples may be purchased by the Federal
agency and supplied to the collector, or purchased by the collector and
submitted to a laboratory with an agency's specimens. Each blind sample is
submitted as if it were a donor specimen. This requires the collector to
complete a Federal CCF and to properly label the specimen bottle(s) containing
the sample. Since there is no donor associated with a blind sample, the
collector generates a fictitious social security number or employee
identification number and fictitious initials to be written on the specimen
bottle label/seal.
The collector or the Federal agency, whichever
purchased the blind samples, must forward information to the MRO, so he or she
will have the information necessary to determine if the laboratory reported the
correct result. On the MRO Copy of the Federal CCF, the collector indicates
that the sample is a "blind QC sample" where the donor would normally provide a
signature (Step 5 on Copy 2 of the Federal CCF).
An incorrect result reported by the laboratory does
not automatically indicate that the laboratory made an analytical error. For
example, there could have been a problem with the sample itself (e.g.,
stability, concentration) or the collector did not properly submit the sample.
When a laboratory reports a result different from the
one expected based on information provided by the supplier of the blind sample,
the MRO must contact the Federal agency. The Federal agency will investigate
and/or contact the appropriate regulatory office to institute an investigation
to determine the exact cause of the incorrect result. When the specific cause
is identified, appropriate corrective actions will be taken. The regulatory
office will share the findings with the MRO.
B. Shy Bladder
Occasionally, a donor is unable to provide a specimen
upon arrival at the collection site because he or she either urinated recently
or has "shy bladder". Generally, the term "shy bladder" refers to an individual
who is unable to provide a urine specimen either upon demand or when someone is
nearby during the attempted urination.
When a donor has difficulty providing a urine
specimen, the collector gives the donor a reasonable amount of liquid to drink
over a period of time (not to exceed 3 hours). Unsupported claims of
"situational anxiety" or dehydration are not considered valid reasons for a
donor's failure to provide a urine specimen. When sufficient time has elapsed
and fluids have been ingested, the inability to provide a urine specimen shall
be regarded as a refusal to take a test.
If it is believed that an individual has a "shy
bladder," the Federal agency must arrange to have the donor evaluated to
determine whether the donor's inability to provide a specimen is genuine or
constitutes a refusal to provide a specimen. The evaluation must be performed
by a licensed physician (e.g., the MRO, a physician acceptable to the agency,
the agency's occupational health physician) and must take place as soon as
practical after the attempted collection.
The examining physician must determine, in his or her reasonable medical
judgment, that a medical condition has or, with a high degree of probability,
could have precluded the donor from providing a urine specimen (e.g., a urinary
system dysfunction or a documented pre-existing psychological disorder). An
evaluation must include a review of any pertinent medical records and may
include evaluative testing such as blood chemistries for kidney function or
other physiologic factors likely to affect urine output.
The examining physician shall provide to the MRO a
brief written statement describing his or her conclusion and the basis for it.
The written statement shall not include detailed information on the medical
condition of the donor. Upon receipt of the written statement from the
examining physician, the MRO shall report his or her conclusions to the agency
in writing.
C. Occupational and Public Safety
Executive Order 12564 uses the term "illegal drugs" to
refer to any controlled substance included in Schedule I or II of the
Controlled Substances Act, and not to refer to the use of a controlled
substance pursuant to a valid prescription or other uses authorized by law.
The purpose of this policy is to ensure that a
workplace drug testing program does not intentionally identify an individual
who is receiving valid medical care and, thereby, provide confidential medical
information to an agency or anyone else.
There is, however, a public safety issue associated
with information that a donor may provide to an MRO during the review of a test
result. That is, the donor may be taking a legal prescription medication as
treatment for a medical condition and the medication may have possible side
effects that may impair the mental and/or physical abilities required for the
performance of potentially hazardous tasks (e.g., driving a car or truck,
operating machinery).
If the side effects of a legitimately prescribed
medication have a possible impact on the safety aspects of the work performed
by a donor, the MRO must decide what must be done with the information.
Although the Mandatory Guidelines require an MRO to verify a drug test result
as a negative result if the donor has legally taken a prescription medication,
it is recommended that the MRO contact the prescribing physician to discuss the
possible impact that the medication may have on the safety aspects of the work
performed by the donor. Additionally, some occupations have restrictions that
prohibit an individual from taking specific medications that may, otherwise, be
allowable for other occupations. In these instances, the MRO may inform the
individual responsible for certifying that the donor is qualified to perform
that job that the donor is taking a medication that is restricted for an
individual in that occupation or that the medication may affect the
individual's ability to perform a safety sensitive occupation.
D. Donor Rights to Information
An employee who is the subject of a drug test may,
upon written request through the MRO and the Federal agency, have access to any
records relating to his or her drug test, any records relating to the results
of any relevant certification, review, or revocation of certification
proceedings, and access to a documentation package. A donor or Federal agency
will occasionally request the testing laboratory to provide a complete package
of analytical data, chain of custody records, and other administrative
documents associated with the testing of a particular specimen. This package is
generally referred to as a "data package" or "litigation package." The request
must always be submitted to the laboratory through the MRO.
A standard data package provided by an HHS-certified
laboratory consists of the following items:
-
A cover sheet that provides a brief description of
the drug testing procedures and specimen validity tests performed on the
donor's specimen
-
A table of contents page that lists by page number
all documents and materials in the package
-
A copy of the Federal CCF with any attachments and a
copy of the electronic report (if any) generated by the laboratory
-
A brief description of the initial drug tests and
initial specimen validity tests (e.g., instrumentation, batch quality control,
and test data format)
-
A brief description of confirmatory drug tests and
confirmatory validity tests (e.g., instrumentation, batch quality control, and
test data format)
-
A copy of the resume or curriculum vitae for the
certifying scientist that certified the test result
-
A copy of the resume or curriculum vitae for the
laboratory's Responsible Person(s)
-
Donor specific information including:
-
Internal chain of custody records for the specimen,
-
Memoranda (if any) generated by the laboratory,
-
Copies of the initial drug and specimen validity test
data for the donor's specimen with all calibrators and controls identified and
copies of all internal chain of custody documents related to the initial tests,
and
-
Copies of the confirmatory drug and specimen validity
test data for the donor's specimen with all calibrators and controls identified
and copies of all internal chain of custody documents related to the
confirmatory tests.
Appendix A. Laboratory
Reporting Criteria
Positive
A laboratory will report a urine specimen as positive for a drug/drug
metabolite when:
-
The specimen's immunoassay result was at or above the
initial test cutoff for the drug class and
-
The specimen's GC/MS result (i.e., on a separate
aliquot) was at or above the confirmatory test cutoff for the specific
drug/drug metabolite.
Drug/Metabolite |
Initial Test Cutoff |
Confirmatory Test Cutoff |
Amphetamines |
1000 ng/mL |
Amphetamine 500 ng/mL |
Methamphetamine 500 ng/mL*
*must also contain at least 200 ng/mL amphetamine
|
Opiates |
2000 ng/mL |
Codeine 2000 ng/mL |
Morphine 2000 ng/mL |
6-acetylmorphine 10 ng/mL*
*must also be positive for morphine |
Marijuana (cannabinoids) |
50 ng/mL |
THCA (marijuana metabolite) 15 |
Cocaine |
300 ng/mL |
Benzoylecgonine (cocaine metabolite) 150 ng/mL |
Phencyclidine (PCP) |
25 ng/mL |
Phencyclidine 25 ng/mL |
Negative
A laboratory will report a urine specimen as negative when the specimen has
valid negative drug test results at any point in the testing process:
-
Immunoassay results below the initial test cutoffs,or
-
GC/MS results below the confirmatory test cutoffs, and
-
Specimen validity test results in the acceptable
range
Dilute
A laboratory will report a urine specimen as dilute in conjunction with
a positive or negative drug test when on a single aliquot:
-
The creatinine concentration is greater than or equal
to 2 mg/dL and less than 20 mg/dL, and
-
The specific gravity is greater than 1.0010 but less
than 1.0030
Substituted
A laboratory will report a urine specimen as substituted when both the
initial and confirmatory tests (i.e., tests on separate aliquots) document
that:
-
The creatinine concentration is less than 2 mg/dL, and
-
The specific gravity is less than or equal to 1.0010 or
greater than or equal to 1.0200
Adulterated
A laboratory will report a urine specimen as adulterated when both the
initial and confirmatory test results (i.e., tests on separate aliquots) meet
one of the following criteria:
-
The pH is less than 3,
-
The pH is greater than or equal to 11,
-
The nitrite concentration is greater than or equal to
500 mcg/mL,
-
Chromium (VI) is present, verified by a specific
confirmatory test,
-
A halogen (e.g., bleach, iodine, fluoride) is
present, verified by a specific confirmatory test,
-
Glutaraldehyde is present (verified by a GC/MS
confirmatory test),
-
Pyridine (pyridinium chlorochromate) is present
(verified by a GC/MS confirmatory test),
-
A surfactant is present (i.e., dodecylbenzene
sulfonate-equivalent concentration is greater than or equal to 100 mcg/mL),
-
The specimen contains a substance that is not a
normal constituent of human urine (verified by a confirmatory test for the
specific substance), or
-
The specimen contains an endogenous substance at a
concentration that is not a normal physiological concentration (verified by a
confirmatory test for the specific substance).
Invalid Result
A laboratory will report an invalid result for a urine specimen when results
for two separate aliquots meet one of the following criteria:
1. Creatinine concentration and specific gravity
results are discrepant:
-
The creatinine concentration is less than 2 mg/dL on
both the initial and confirmatory creatinine tests and the specific gravity is
greater than 1.0010 but less than 1.0200 on either or both the initial and
confirmatory specific gravity tests, or
-
The specific gravity is less than or equal to 1.0010
on both the initial and confirmatory specific gravity tests and the creatinine
concentration is greater than or equal to 2 mg/dL on either or both the initial
and confirmatory creatinine tests;
2. The pH is outside the acceptable range:
-
The pH result is greater than or equal to 3 and less
than 4.5 using either a colorimetric pH test or pH meter for the initial test
and a pH meter for the confirmatory test, or
-
The pH result is greater than or equal to 9 and less
than 11 using either a colorimetric pH test or pH meter for the initial test
and a pH meter for the confirmatory test;
3. Nitrite is present, but below the program cutoff
for adulteration:
-
Nitrite is greater than or equal to 200 mcg/mL using
a nitrite colorimetric test for both the initial and confirmatory tests,
-
Nitrite is greater than or equal to the equivalent of
200 mcg/mL nitrite using a general oxidant colorimetric test for both the
initial and confirmatory tests, or
-
Nitrite is greater than or equal to 200 mcg/mL using
a nitrite colorimetric test or a general oxidant colorimetric test and is
greater than or equal to 200 mcg/mL but less than 500 mcg/mL for a confirmatory
test using a different method;
4. The possible presence of chromium (VI) is
determined using the same chromium (VI) colorimetric test with a cutoff greater
than or equal to 50 mcg/mL chromium (VI) for both the initial and confirmatory
tests;
5. The possible presence of a halogen (e.g., bleach,
iodine, fluoride) is determined using the same halogen colorimetric test with a
cutoff greater than or equal to the LOD for both the initial and confirmatory
tests, or relying on the odor of the specimen as the initial test;
6. The possible presence of glutaraldehyde is
determined by using the same aldehyde test (aldehyde present) or characteristic
immunoassay response on one or more drug immunoassay tests for both the initial
and confirmatory tests;
7. The possible presence of an oxidizing adulterant is
determined by using the same general oxidant colorimetric test (with a greater
than or equal to 200 mcg/mL nitrite-equivalent cutoff, a greater than or equal
to 50 mcg/mL chromium (VI)-equivalent cutoff, or a halogen concentration
greater than or equal to the LOD) for both the initial and confirmatory tests;
8. The possible presence of a surfactant is determined
by using the same surfactant colorimetric test with a greater than or equal to
100 mcg/mL dodecylbenzene sulfonate-equivalent cutoff for both the initial and
confirmatory tests, or using a foam/shake test for the initial test;
9. Interference occurs on the immunoassay drug tests
on two separate aliquots (i.e., valid immunoassay drug test results cannot be
obtained);
Note: Tolectin® (Tolmetin - a non-steroidal
anti-inflammatory), Flagyl® (metronidazole - an antifungal and antibacterial
agent), Cipro® (ciprofloxacin - an antibacterial agent), Grisactin®
(Griseofulvin - a fungistatic antibiotic), and Clonoril® (sulindac - a
non-steroidal anti-inflammatory) are some known prescription medications that
may interfere with some immunoassay tests.
10. Interference with the GC/MS drug confirmation
assay occurs on two separate aliquots of the specimen and the laboratory is
unable to identify the interfering substance;.
11. The physical appearance of the specimen is such
that testing the system may damage the laboratory=s instruments; or
12. If the physical appearances of Bottles A and B are
clearly different, the test result for Bottle A is one of the reasons stated in
1 through 10 above and/or the specimen was negative for drugs upon initial
testing.
Table 1. Immunoassays
Method |
Abbreviation |
Description |
Enzyme Immunoassay |
EIA |
An immunoassay based on competition for
antibody binding sites between drug in the specimen and drug labeled with an
enzyme. Enzyme activity decreases upon binding to the antibody, so the drug
concentration in the specimen can be measured in terms of enzyme activity. |
Kinetic Interaction of Microparticles in
Solution |
KIMS |
An immunoassay based on the principle of
the kinetic interaction of microparticles in a solution where the drug content
of the urine is directly proportional to the inhibition of the microparticle
aggregation. |
Cloned Enzyme Donor Immunoassay |
CEDIA |
An immunoassay utilizing enzyme
fragments engineered by recombinant DNA techniques. Two fragments, the enzyme
donor (ED) and enzyme acceptor (EA), are inactive when separated. CEDIA is
based on competition for antibody binding sites between drug conjugated with ED
and drug in the specimen. Enzyme activity decreases when the ED-drug fragment
is bound, so the drug concentration in the specimen can be measured in terms of
enzyme activity (i.e., drug concentration and enzyme activity are inversely
related). |
Fluorescence Polarization Immunoassay |
FPIA |
An immunoassay based on competition
between drug in the specimen and drug labeled with a fluorophore. Light emitted
by the fluorescently labeled drug/antibody complex will be more polarized. The
specimen's fluorescence polarization value is inversely related to the drug
concentration. |
Radioimmunoassay |
RIA |
An immunoassay based on competition
between drug in the specimen and drug labeled with a radioisotope. The
antibody-antigen complex is precipitated out of solution, separated from the
unbound reagents, and measured in a gamma counter. Radioactivity is inversely
proportional to drug concentration. |
Microplate Enzyme-Linked Immunosorbent
Assay |
ELISA |
A competitive binding enzyme immunoassay
using drug-specific antibodies immobilized on the sides of a microplate well. |
Table 2. Laboratory Specimen Validity
Test Methods
Method |
Analytes |
Description |
Colorimetry |
pH, creatinine, adulterants (general or
compound-specific tests) |
An analytical procedure based on
comparison of the color developed in a solution of a test material with that in
a standard solution, quantitated on the basis of the absorption of light. In a
colorimetric test method, reagents are added to a sample and a reaction occurs
with the analyte of interest, producing a color. Because the intensity of the
color is related to the analyte's concentration, the concentration of the
analyte is determined by visually measuring the color or electronically
measuring the intensity of light at selected wavelengths (i.e.,
spectrophotometry). |
Refractometry |
Urine specific gravity |
A urine specific gravity refractometer
is used to determine the amount of solute (i.e., urinary total solids) in the
urine by measuring the index of refraction. The index of refraction is the
ratio of electromagnetic radiation in a vacuum to its velocity in the medium of
interest. The instrument manufacturer applies a formula to convert from
refractive indices to the urine specific gravity values displayed by the
refractometer. |
Potentiometry |
pH |
The measurement of the electrical
potential difference between two electrodes in an electrochemical cell. A pH
meter is a type of potentiometer. |
Atomic Absorption Spectrophotometry
(AAS) |
Adulterants (e.g., chromium VI) |
An analytical method in which a sample
is vaporized in a flame or graphite furnace. The atoms absorb ultraviolet or
visible light and make transitions to higher electronic energy levels. The
analyte concentration is determined from the amount of absorption of specific
wavelengths. |
Electrophoresis
Capillary electrophoresis (CE)
|
Adulterants (e.g., nitrite,
chromium VI) |
A separation technique that
is based on the mobility of ions in an electric field. Positively charged ions
migrate towards a negative electrode and negatively charged ions migrate toward
a positive electrode. Ions have different migration rates depending on their
total charge, size, and shape, and can therefore be separated. Capillary
electrophoresis (CE) is an electrophoretic method using a small-bore, fused
silica capillary tube. The capillary tube allows the use of very high electric
fields because the small capillaries efficiently dissipate the heat that is
produced. Increasing the electric fields produces very efficient separations
and reduces separation times. |
Gas Chromatography/Mass Spectrometry
(GC/MS) |
Adulterants (e.g., glutaraldehyde,
pyridine) |
(See method description in this manual) |
Inductively-Coupled Plasma-Mass
Spectrometry (ICP-MS) |
Adulterants (e.g., chromium VI,
halogens) |
An analytical method in which the sample
is introduced into a radio-frequency (RF) induced plasma in the form of a
solution, vapor or solid. The temperature of the plasma may reach up to 6000 K
at the center and 8000 K at its periphery. The high thermal energy and
electron-rich environment of the ICP results in the conversion of most atoms
into ions. A quadrupole mass spectrometer permits the detection of ions at each
mass in rapid sequence, allowing signals of individual isotopes of an element
to be scanned. |
Multi-wavelength spectrometry (MWS) |
Adulterants (e.g., nitrite, chromium VI,
halogens, surfactants) |
A method that measures multiple
wavelengths of light (or other electronic transmissions) to identify an
analyte. The method generates corrected absorbance values that are related to
the analyte concentration. |
Ion Chromatography (IC) |
Adulterants (e.g., nitrite, chromium VI,
halogens) |
A form of liquid chromatography that
uses ion-exchange resins to separate atomic or molecular ions based on their
interaction with the resin. Its greatest utility is for analysis of anions for
which there are no other rapid analytical methods. It is also commonly used for
cations and biochemical species such as amino acids and proteins. |
High-Performance Liquid Chromatography
(HPLC) |
Adulterants (e.g., nitrite, chromium VI) |
A chromatographic technique for
separating and analyzing chemical substances in solution. Separation is based
on absorption, partition, ion exchange, or size exclusion. |
Table 3. Some Products Containing
Opiates
Drug |
Prescription Products |
Non-Prescription Products1 |
Codeine |
Ambenyl with Codeine® |
Kaodene with Codeine® |
Codimal PH7 Syrup® |
|
Fioricet with Codeine® |
|
Fiorinal with Codeine® |
|
Guiatuss A.C. ® |
|
Phenaphen with Codeine® |
|
Robitussin-DAC® |
|
Triacin-C® |
|
Tylenol with Codeine® |
|
Morphine |
Avinza® |
Donnagel-PG®2 |
Astramorph PF® |
Infantol Pink®2 |
Depodur® |
Kaodene with Paregoric®2,3 |
Duramorph® |
Quiagel PG®2 |
Kadian® |
|
MS Contin Tablets® |
|
Oramorph SR® |
|
Roxanol® |
|
Paregoric®3 |
|
1Each listed non-prescription product is used as an
anti-diarrheal. They are generally availably over-the-counter; however,
non-prescription sale is prohibited in some States. 2The non-prescription
morphine products listed contain opium. 3Paregoric alone is a Schedule III
prescription drug, but in combination with other substances is a Schedule V
over-the-counter product.
Table 4. Some Products Containing
Amphetamines
|
Products |
Substances known to contain d-amphetamine
or racemic d,l-amphetamine |
Adderall® |
Dexedrine® |
DextroStat® |
Substances known to contain d-methamphetamine |
Desoxyn® |
Substances known to metabolize to
methamphetamine (and amphetamine) |
Benzphetamine (Didrex®) |
Dimethylamphetamine |
Famprofazone |
Fencamine |
Furfenorex |
Selegiline (Alzene®, Carbex®, Deprenyl®, Eldepryl®) |
Substances known to metabolize to
amphetamine |
Amphetaminil |
Clobenzorex |
Ethylamphetamine |
Fenethylline |
Fenproporex |
Mefenorex |
Mesocarb |
Prenylamine |
Table 5. MRO Actions for Single
Specimen/Bottle A Reports
Laboratory Result |
MRO Action |
Negative |
Report the negative result. |
Negative and Dilute |
Report the negative result and inform the
Federal agency that the next time the donor is selected for a drug test, the
agency may require the specimen to be collected using a direct observed
collection procedure. |
Positive |
Contact the donor to determine if he or she has a
valid medical explanation for the positive result. If the medical explanation
for the positive result appears to be:
a. Legitimate - Verify the result as negative and
report a negative result to the agency.
(It is recommended that the MRO contact the prescribing physician to discuss
the possible impact that the medication may have on the safety aspects of the
work performed by the donor. The MRO may inform the Federal agency's designated
representative that the donor is taking a medication that is restricted for an
individual in that occupation or that the medication may affect the
individual's ability to perform a safety sensitive occupation.)
b. Not legitimate - Report the positive drug result to
the Federal agency.
|
Positive and Dilute |
If the positive drug test is verified as negative due
to a valid medical explanation - Report the specimen as negative and dilute
and inform the Federal agency that the next time the donor is selected for a
drug test the agency may require the specimen to be collected using a direct
observed collection procedure.
If the positive drug test is verified positive -
Report the positive result to the Federal agency but do not report that
the specimen was also dilute.
|
Substituted |
Contact the donor to determine if he or she has a
valid medical explanation for the substituted result. If the medical
explanation for the substituted result appears to be:
a. Legitimate - Report a negative result to the
Federal agency.
b. Not legitimate - Report a refusal to test (substituted) to the Federal
agency.
|
Adulterated |
Contact the donor to determine if he or she has a
valid medical explanation for the adulterated result (Although the MRO is
required to contact the donor and give the donor an opportunity to explain the
adulterated result, the program criteria for adulteration definitively proves
adulteration. There is no valid medical explanation.) - Report a refusal to
test (adulterated) to the Federal agency. |
Invalid Result |
Prior to reporting an invalid result to the MRO, the
laboratory must contact the MRO to decide whether additional/different testing
would be of use to obtain a definitive result
Contact the donor to determine if he or she has an
explanation for the invalid result.
-
If the medical explanation for a first invalid result
appears to be:
a. Legitimate - Report the test as canceled with the
reason for the invalid result and inform the Federal agency that a recollection
is not required because the explanation provided by the donor for the
invalid result is acceptable unless a negative drug test result is required
based on the reason for testing (e.g., pre-employment, return to duty,
follow-up).
b. Not legitimate - Report the test as canceled with the reason for the invalid
result and direct the Federal agency to immediately collect another specimen
using a direct observed collection procedure.
-
If a specimen is recollected using direct observation
and is invalid due to:
a. The same reason reported for the first specimen -
Report the canceled test with the reason for the invalid result and recommend
to the Federal agency that no further action be taken.
b. A different reason than reported for the first specimen - Report the result
for the recollected specimen as a refusal to test with the reason for the
invalid result. (The reason for reporting a refusal to test rather than
reporting another invalid result is that the donor must have managed to defeat
the drug test even though a direct observed collection procedure was used.)
|
Multiple Non-Negative Results |
Follow the review procedures above as appropriate for
each reported result and report all verified results. |
Rejected for Testing |
Report the test as canceled along with the reason for
the cancellation and inform the Federal agency that an immediate collection of
another specimen is permitted, if a negative drug test result is required based
on the reason for testing (e.g., pre-employment, return to duty, follow-up). |
Table 6. MRO Actions for Retest
Specimen Reports (Bottle B or Aliquot of Bottle A)
Laboratory Retest Result
|
MRO Action
|
Reconfirmed |
Failed to Reconfirm |
Additional Testing Results1 |
|
Drug(s) |
|
|
Report as reconfirmed. |
Adulterated |
|
|
Report as reconfirmed. |
Substituted |
|
|
Report as reconfirmed. |
|
Drug(s) |
Adulterated
Substituted
|
Contact the donor to determine if he or she has an
explanation for the adulterated/ substituted result.
If the explanation for the adulterated/substituted
result appears to be:
-
Legitimate - Report as failed to reconfirm (specify
drug(s)) and cancel both tests.
-
Not legitimate - Give the donor 72 hours to request
that Laboratory A tests Bottle A for the adulterant/substitution.
1. If Bottle A contains the adulterant/is substituted
- Report as refusal to test with the reason (adulterant present/substituted)
2. If the donor chooses not to have Bottle A retested - Report as failed to
reconfirm (specify drug(s)) and as refusal to test with the reason (adulterant
present/substituted)
3. If Bottle A does not reconfirm Bottle B results (i.e., does not contain the
adulterant/is not substituted):
-
Cancel both tests,
-
Direct the Federal agency to immediately collect
another specimen using a direct observed collection procedure, and
-
Notify the appropriate regulatory office about the
failure to reconfirm and cancelled tests.
|
1 Laboratory B conducts specimen validity tests to
determine whether the failure to reconfirm the drug(s) is because the retest
specimen is adulterated/substituted/invalid.
Laboratory Retest Result |
MRO Action |
Reconfirmed |
Failed to Reconfirm |
Additional Testing Results1 |
|
|
Drug(s) |
Invalid |
Prior to reporting as failed to reconfirm and invalid
to the MRO, the laboratory must contact the MRO to decide whether testing at a
third laboratory would be of use to obtain a definitive result.
Assuming the invalid result cannot be resolved:
-
Report as failed to reconfirm (specify drug(s)) with
the reason for the invalid result,
-
Cancel both tests,
Direct the Federal agency to immediately collect another specimen using a
direct observed collection procedure, and
Notify the appropriate regulatory office about the failure to reconfirm and
cancelled tests.
|
|
Drug(s) |
Not adulterated
Not substituted
Not invalid
|
Prior to reporting as failed to reconfirm
to the MRO, if the laboratory believes the drug may be present, the laboratory
must contact the MRO to decide whether testing at a third laboratory would be
useful.
-
Report as failed to reconfirm (specify drug(s)),
-
Cancel both tests, and
-
Notify the appropriate regulatory office about the
failure to reconfirm and cancelled tests.
|
|
Adulterated |
|
-
Report as failed to reconfirm (specify adulterant),
-
Cancel both tests, and
-
Notify the appropriate regulatory office regarding
the test results for the specimen.
|
|
Substituted |
|
-
Report as failed to reconfirm (not substituted),
-
Cancel both tests, and
-
Notify the appropriate regulatory office regarding
the test results for the specimen.
|
1 Laboratory B conducts specimen validity tests to
determine whether the failure to reconfirm the drug(s) is because the retest
specimen is adulterated/substituted/invalid.
When Laboratory A reported multiple non-negative
results (i.e., drug-positive, adulterated, substituted) for the primary
specimen and Laboratory B reconfirmed some but not all of the results for the
retest specimen, the MRO takes the following action:
-
Report all reconfirmed results (specify
drug(s)/adulterant/substituted) and all results that failed to reconfirm
(specify drug(s)/adulterant/not substituted).
-
For specimens with at least one reconfirmed positive
drug, inform the Federal agency that it may take action based on the
reconfirmed drug result(s):
-
Regardless of Laboratory B's failure to reconfirm the
other drug(s) reported positive in the primary specimen
-
Regardless of whether Laboratory B found the retest
specimen to be adulterated, substituted, or invalid when performing SVT after
failing to reconfirm a drug
-
Regardless of whether Laboratory B reported the
failure to reconfirm a drug because the laboratory was unable to obtain valid
confirmatory test results.
-
Notify the appropriate regulatory office of the test
results for the specimen.
|
BIBLIOGRAPHY
1. Baselt, Randal C. 2004. Disposition of Toxic Drugs
and Chemicals in Man, 7th Ed. Foster City, CA, Biomedical Publications.
2. Bastiani, R.J. Urinary Cannabinoid excretion
patterns. In: Agurell, S; Dewey, W.L.; Willette, R.E. eds., The Cannabinoids,
pharmacologic and therapeutic aspects. New York: Raven Press, 1984:263.
3. Dart, Richard C. (Ed.). 2004. Medical Toxicology,
3rd Ed. Philadelphia, PA, Lipincott Williams and Wilkins.
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Julien, Robert M. 1988. A Primer of Drug Action, 5th Ed. New York, NY, W. H.
Freeman and Company.
National Institute on Drug Abuse. 1988. Medical Review
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Nissin, David. 2004. Mosby's Drug Consult. St. Louis,
MO, Mosby, Inc.
Shults, Theodore F. 2002. Medical Review Officer
Handbook, 8th Ed. Research Triangle Park, NC, Quandrangle Research, LLC.
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