Most drugs of abuse in urine (DAU) Drugs of Abuse in Urine Sample Choice, Length
testing have relatively short Drug abuse is usually defined as of Urine Drug Detection
windows of detection periods (up the excessive and persistent use, usu- The laboratory plays a central
to 3 days) except for those with ally by self-administration, of any drug, role in the detection of drugs of
high lipid solubility licit or illicit, which may lead to ad- abuse in human urine specimens.
(benzodiazepines, up to 21 days; verse physical or psychological conse- Urine is the preferred specimen for
cannabinoids, up to 60 days). quences. Drug abuse is not always drug testing primarily because it is
Immunoassays have high sensitivity associated with any degree of non-invasive (in contrast to drawing a
for DAU screening but lower frequency but is often associated with blood specimen, an invasive proce-
specificity because of cross- drug use in quantities which may result dure which may require patient con-
reactivity with substances other in some degree of toxicity in the user sent). Drug levels in blood only
than the drugs in question. and which may reflect a pattern of psy- reflect presence of drug at a given
It is important to establish patterns chopathological behavior.1,2 In fact, point in time, and levels may be high
of drug usage and populations of there is a continuum from minimal use enough to be detected only for a rela-
interest because they may have an to abuse to addictive drug use.3 Most tively short period of time. Urine
impact on which DAU to include in drugs of abuse are regulated by the specimens may contain detectable
screening panels. government, primarily by the schedules levels of drug over an extended pe-
Confirmation of DAU testing is the of the Controlled Substances Act.2 Ex- riod and at much higher concentra-
use of a second analytical method amples of drugs of abuse include de- tions than in blood. Urine may also
to positively identify a drug or pressants (opioids, barbiturates, contain higher levels of drug metabo-
metabolite in urine. benzodiazepines, alcohol), stimulants lites than blood, providing further
(amphetamines, cocaine), hallucino- evidence of drug use. T1 outlines the
Approximately 24 million urine gens (LSD, mescaline, phencyclidine), advantages and disadvantages of
drug tests were performed annually in and cannabinoids (marijuana). urine specimens for DAU testing.2
the United States at a cost of about $1.2
billion per year, according to a 1994
study by the Committee on Drug Use in
the Workplace of the National Research
Urine Drug Testing, Advantages and Disadvantages
Advantages
T1
Council and the Institute of Medicine
and commissioned by the National Insti- Non-invasive
Ample volume
tute on Drug Abuse.1 That number Drugs and drug metabolites found in urine are usually stable
would be expected to be even higher Drugs and their metabolites are often present in higher concentrations in urine than in
now, 10 years later. The service of urine other biological materials
Detectable in urine for relatively long period of time
drug testing is usually provided by the Presence of metabolites (in addition to parent drug) provides further evidence of drug use
clinical laboratory. The laboratory must Readily preserved by refrigeration or freezing
make many crucial decisions with re- Analysis relatively simple because of absence of proteins and cellular material in urine
368 gard to the drugs to test, including the
Wide availability of commercial reagents and analytical systems
Drugs
T3
Duration of Detection in Urine
369
being collected under DOT rules
for an individual previously veri- Alcohol up to 1 day
Amphetamines (including MDMA, MDA) 1-2 days
fied to have a positive DOT test. Barbiturates 1-3 days
Laboratories may also perform a Benzodiazepines Up to 21 days
urine pH determination to verify that Cannabinoids Up to 60 days*
Cocaine 1-3 days
the urine specimen pH is within the Methadone 1-3 days
limits established for healthy human Opiates (including codeine and morphine) 1-3 days
subjects (pH 4.5 to 8.0). After urine Propoxyphene 1-3 days
specimen collection, a documented *At 50 ng/mL cutoff concentration
Assay
T4
Cutoff Concen-
and/or metabolites in urine. In a recent results for amphetamines may also be tration (ng/mL)
College of American Pathologists caused by a number of Amphetamine/
(CAP) survey of laboratories enrolled sympathomimetic drugs including Methamphetamine 1,000
in the CAP urine drug screening pro- ephedrine, pseudoephedrine, and Barbiturate 200
Benzodiazepine 200
gram (UDS), of the approximately phenylpropanolamine, which may be Cannabinoids 50, 100
2,850 laboratories reporting results for present in over-the-counter cold and Cocaine Metabolite 300
cocaine and metabolites, the CAP decongestant medications.13 Methadone 300
Opiates 300, 2000
breakdown on laboratory methods False-positive results for common Propoxyphene 300
showed that about 44% of laboratories opiate screening assays are encountered
used an enzyme immunoassay in patients receiving antibiotics of the
technique, 39% of laboratories used a quinolone class that crossreact with the
fluorescent immunoassay, and 12% opiate immunoassay.14 Poppy-seed positive screening rate for 8 DAU
used a point-of-care assay.10 food products, such as poppy-seed screening tests was determined, result-
The initial screening DAU assay is bagels or muffins, may cause a true- ing in a proposal to standardize the
used by the laboratory to eliminate positive immunoassay screening test DAU panel to 3 DAU tests, excluding
urine specimens which are below the for opiates due to the presence of low, DAU tests with very low positive
cutoff concentration for that drug or but still detectible, levels of opium al- screening rate or a DAU test needed
drug class. The cutoff concentration, kaloids.15 A screening cutoff of 2,000 specifically for methadone. The study
used to separate negative specimens ng of morphine is often used to elimi- showed that after the adoption of a stan-
from specimens which require further nate positives due strictly to poppy dard DAU panel, there was a 47% de-
testing, will vary according to the seed ingestion; however, a substantial crease in DAU utilization and costs.19
screening technique used, the manu- number of positives due to true opiate
facturers recommendations, and the abuse will also be missed at this high DAU Confirmation Testing
laboratorys policy. Usually, the cutoff cut-off level. and Analytical Procedures
concentration will be the concentration Confirmation of DAU testing is
of the lowest calibrator provided by Patterns of Drugs of Abuse defined as a second test by an alternate
the manufacturer. T4 provides cutoff Usage and Drug Screening chemical method to positively identify
concentrations for the enzyme multiple Panels a drug or metabolite. Confirmation test-
immunoassay technique (EMIT, Syva, Drugs-of-abuse usage may differ ing is carried out on presumptive posi-
Dade Behring) for some common significantly depending on the popula- tive specimens as determined by the
DAU assays. tion of interest [ie, age, environment initial immunoassay screens.20 The se-
Immunoassays are widely used by (urban versus rural), geographical areas lection of the analytical method for
clinical laboratories in the United (United States versus other countries), confirming the presence or absence of
States because they are inexpensive, etc].16-18 For example, methampheta- drugs or metabolites in a specimen will
rapid, easily automated, and have high mine abuse is much more common on depend on the purpose of the DAU
sensitivity for detection of DAU. The the West Coast than the East Coast, al- testing. If drug-testing results are used
major weakness in the immunoassay though the drug is slowly spreading as a guide in medical diagnosis or in
screening techniques for DAU is the eastward.18 patient therapy and do not affect the
less-than-perfect specificity for their It is important to determine drugs- test subject adversely, it may be unnec-
designated drug(s) of abuse. There may of-abuse usage patterns in a particular essary to confirm in order to establish
be cross-reactivity due to the presence population, since it may have a signifi- unequivocally the presence of the ini-
of substances other than the analyte(s) cant impact on use and costs for DAU tially positive DAU. In cases where
of interest (false-positive result). The screening testing. Many laboratories further testing is desired, a second pre-
370 degree of cross-reactivity with have set up DAU panels for clinician sumptive determination involving a
substances other than the drug of inter- convenience and to facilitate the order- repeat of the immunoassay screening
est will vary from assay to assay. Also, ing of DAU screening. However, the may be all that is required.2 It should
there may be variable cross-reactivity widespread use of DAU panels may be emphasized that the performance of
to a parent drug and its metabolites, have unintentionally led to over-utiliza- the second presumptive determination
thus making it extremely difficult to tion and unnecessary drug testing, espe- is not a substitute for confirmatory test-
determine all possible substances cially given the ease of ordering a panel ing but is designed to reduce operator
which may cause a false-positive reac- with many DAU drugs when perhaps a errors that can cause false-positive re-
tion. For example, a metabolite of rani- much smaller panel of fewer DAU sults. When a repeat of the assay is not
tidine crossreacts with the would suffice.19 In a recent study, the sufficient, a second, confirmatory,
POSITIVE
Purpose of Testing
373