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Urine drug screens
Screening Methods
Urine drug screens are generally performed using either immunoassays or gas chromatography-mass
spectrometry (GC-MS).2 Immunoassay UDS contain specific antibodies against common drugs of abuse and
their metabolites. The immunoassay is the most commonly used UDS because it is inexpensive and rapid. Five
different immunoassays are available: cloned enzyme donor immunoassay, enzyme-multiplied immunoassay
(EMIT), fluorescence polarization immunoassay (FPIA), and immunoturbidimetic assay radioimmunoassay
(RIA). The substances most commonly tested by a typical immunoassay include amphetamines, cannabinoid
metabolites, cocaine metabolites, opiate metabolites, and phencyclidine (PCP). Expanded immunoassays are
available to test for tricyclic antidepressants, barbiturates, methadone, alcohol, and benzodiazepines and may be
beneficial when use of these substances is suspected. One major problem with immunoassays is a false-positive
result. Therefore, a more specific confirmatory test, such as GC-MS, is needed to confirm a positive finding
with an immunoassay. GC-MS is more accurate than an immunoassay, but it is more expensive and time
consuming.1 GC-MS breaks down drug molecules into ionized fragments and identifies substances based on
mass-to-charge ratio using a mass spectrometer.
Although blood, hair, nails, or saliva can be used, most screening is done using urine samples.2 Ease of
collection, higher drug concentrations, and longer durations of detection are primary reasons for using urine
samples for drug screening. Table 1 lists common drugs of abuse and their duration of detection in the urine.
Table 1. Length of time drugs of abuse can be detected in the urine.1,2
Drug/drug class
Alcohol
Amphetamine
Methamphetamine
Barbiturates
Short-acting
Long-acting
Benzodiazepine
Short-acting
Long-acting
Cocaine metabolites
Detection time
7 to 12 hours
48 hours
48 hours
24 hours
3 weeks
3 days
30 days
2 to 4 days
Drug/drug class
Marijuana
Single use
Moderate use (4x/week)
Daily use
Long-term heavy smoker
Opiates
Codeine
Heroin (morphine)
Hydromorphone
Methadone
Morphine
Oxycodone
Propoxyphene
Phencyclidine
Detection time
3 days
5 to 7 days
10 to 15 days
>30 days
48 hours
2 to 4 days
2 to 4 days
3 days
48 to 72 hours
2 to 4 days
6 to 48 hours
8 days
Collection Methods and Criteria
Proper urine collection methods must be used to avoid false-negative results. Urine should be collected in a
tamper-evident container under supervision if necessary.1 Criteria for legitimate urine samples include:
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A volume of 30 mL or more
Temperature between 32▫C and 38▫C
pH of 4.5 to 8.5
Nitrates <500 mcg/mL
Specific gravity >1.002 and <1.020
Creatinine >20 mg/dL
Urine samples with characteristics outside of these ranges, or with a cloudy or dark appearance, may be
adulterated in some manner, either diluted or substituted.
Urine Drug Test Results
The United States Department of Health and Human Services (DHHS) sets the threshold for drug
concentrations for detection by UDS.2 Drug concentrations in the urine below this level are reported as
negative. Table 2 contains a list of these values. However, despite standardization, inaccurate results can occur.
Table 2. Standard threshold levels for screening and confirmatory tests 1,3
Drug/drug class
Amphetamine and
methamphetamine
Barbiturates
Benzodiazepines
Cocaine metabolite
(benzoylecgonine)
Marijuana metabolites (delta-9tetrahydrocannabinol-9carboxylic acid)
Methadone
Opiates (codeine and morphine)
Phencyclidine
Propoxyphene
a
Immunoassay screena (ng/mL) GC/MS confirmationa (ng/mL)
1000
500
300
300
300
200
200
150
50
15
300
2,000
25
300
200
2,000
25
200
Standard cutoff levels; alternate cutoff levels may be available.
Abbreviation: GC-MS, Gas chromatography-mass spectrometry.
False-Negative Results
False negatives are uncommon but can occur as a result of low drug concentrations in the urine, tampering, and
in other situations. Possible reasons for false-negative results include: 1,2
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Dilute urine (excess fluid intake, diuretic use, pediatric sample)
Infrequent drug use
Prolonged time since last use
Recent ingestion
Insufficient quantity ingested
Metabolic factors
Inappropriate test used
Elevated urine lactate
Tampering
o Tetrahydrozoline (eye drops)
o Bleach
o Vinegar
o Soap
o Ammonia
o Lemon juice
o Drain cleaner
o Table salt
o Various chemicals (glutaraldehyde, sodium or potassium nitrate, pyridinium chlorochromate, and
peroxide/peroxidase)
Understanding the UDS and ordering the appropriate test can prevent false-negative results. Results from an
immunoassay or a GC-MS can be deceiving, as these tests may not be able to detect every drug in a particular
drug class.2 This particularly pertains to the opiate and amphetamine/methamphetamine immunoassays. For
example, a test for opiates will detect morphine and drugs that are metabolized to morphine, such as codeine
and heroin. Heroin itself can only be detected for up to 8 hours after use. After 8 hours, only the morphine
metabolite of heroin will be detected in the urine by immunoassay or by GC-MS. Other opiates such as
fentanyl, oxycodone, methadone, hydrocodone, buprenorphine, and tramadol will not be detected and require an
expanded immunoassay panel for detection.1 The amphetamine/ methamphetamine immunoassay can detect
racemic compounds (dextroamphetamine, methamphetamine) and illicit analogues
(methylenedioxyethylamphetamine, methylenedioxyamphetamine, and methylenedioxymethylamphetamine
[MDMA]). This assay, however, has a low sensitivity for MDMA and a more specific test should be performed
if MDMA is suspected.
False-Positive Results
Although immunoassays are very sensitive to the presence of drugs and drug metabolites, specificity and
accuracy varies depending on the assay used and the substance for detection.2 This limitation may result in
false-positives from substances cross-reacting with the immunoassay. Positive results seen on immunoassay
need to be confirmed using the more accurate GC-MS, the forensic standard. The DHHS detection limits reduce
false-positive results, but do not eliminate them. In 1998, the cut-off for opiates was raised from 300 ng/mL to
2000 ng/mL to avoid false positives from poppy seed ingestion. However, these more stringent requirements
can lead to false-negatives and many laboratories continue to use the lower value for detection. For example,
detectable levels of cannabinoids after ingestion of hemp-containing foods with immunoassay have been
reported. Levels of cannabinoids in these samples, however, were not detectable with GC-MS. Passive
marijuana or cocaine smoke inhalation has never been documented to achieve detectable urine concentrations in
adults, however, passive cocaine smoke inhalation has achieved detectable levels in pediatric cases.
GC-MS is very accurate; however, it is not without problems in drug detection.2 As mentioned earlier, heroin
and hydrocodone are metabolized into morphine and hydromorphone respectively, and GC-MS may identify the
metabolites rather than the parent compound. Selegiline is metabolized to l-amphetamine and lmethamphetamine, isomers without central nervous system stimulation. Neither immunoassay nor GC-MS can
differentiate between the l and d isomers and a positive result for amphetamines will be found; an alternative
test, chiral chromatography, may be needed.
Many prescription and nonprescription substances have been reported to cross-react with immunoassays and
cause false-positives.2 Most have only been documented in case reports. Table 3 lists substances reported to
cause false-positive results using immunoassay. This list may not include all potential substances. The
frequency of false-positives varies, depending on the specificity of immunoassay used and the substance under
detection. Immunoassay results for cannabinoid and cocaine metabolites are associated with very few falsepositives while immunoassay results for amphetamines and opiates are associated with a higher number of
false-positives.1
Table 3. Substances that may cause false-positives on immunoassay urine drug screens.1-7
Drug/drug class
Interfering drug
Amphetamine and Amantadine
methamphetamine Brompheniramine
Bupropion
Chlorpromazine
Desipramine
Desoxyephedrine
Ephedrine
Fluoxetine
Isometheptene
Isoxsuprine
Labetalol
Phentermine
Phenylephrine
Phenylpropanolamine
Promethazine
Pseudoephedrine
Ranitidine
Selegiline
Thioridazine
Trazodone
Trimethobenzamide
Trimipramine
Vicks inhalerb
Barbiturates
Ibuprofen
Naproxen
Benzodiazepines Oxaprozin
Sertraline
Cannabinoids
Dronabinol
Efavirenz
Hemp-containing foods
Ibuprofen
Ketoprofen
Naproxen
Piroxicam
Promethazine
Proton pump inhibitorsc
Sulindac
Tolmetin
a
Drug/drug class
Cocaine
Interfering drug
Amoxicillin
Coca leaf teas
Tonic water
Methadone
Chlorpromazine
Clomipramine
Diphenhydramine
Doxylamine
Ibuprofen
Quetiapine
Thioridazine
Verapamil
Opiates
Dextromethorphan
Diphenhydramine
Fluoroquinolonesa
Poppy seeds and oil
Rifampin
Quinine
Phencyclidine
Dextroamphetamine
Dextromethorphan
Diphenhydramine
Doxylamine
Ibuprofen
Imipramine
Ketamine
Meperidine
Thioridazine
Tramadol
Venlafaxine
Tricyclic
Carbamazepine
antidepressants
Cyclobenzaprine
Cyproheptadine
Diphenhydramine
Hydroxyzine
Quetiapine
Lyseric acid
Amitriptyline
diethylamine (LSD) Dicyclomine
Ergotamine
Promethazine
Sumatriptan
Ciprofloxacin, levofloxacin, and ofloxacin.
Vicks inhaler due to l-methamphetamine content interfered with older immunoassays; interference has not
been seen with new enzyme multiplied immunoassay tests (EMIT).
c
Pantoprazole.
b
Summary
The strengths and limitations of UDS need to be fully understood in order to perform the correct screen and also
to correctly interpret the results. All positive results on immunoassay are presumptive until confirmed using
GC-MS. An extensive medication history including prescription, nonprescription, and herbal medications
should be obtained from the patient. Medication histories are important in order to anticipate false-positives as
well as differentiate between drugs used for legitimate medical purposes and drugs of abuse.
References
1. Standridge JB, Adams SM, Zotos AP. Urine drug screen: a valuable office procedure. Am Fam Physician.
2010;81(5):635-640.
2. Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc.
2008;83(1):66-76.
3. Quest Diagnostics. Standard urine testing for drug and alcohol abuse.
www.questdiagnostics.com/employersolutions/standard_urine_testing_es.html
Accessed Nov 11, 2010.
4. Vincent EC, Zebelman A, Goodwin C. What common substances can cause false positives on urine drug
screens for drugs of abuse? J Fam Pract. 2006;55(10):893-894, 897.
5. Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA. Commonly prescribed medications and potential
false-positive urine drug screens. Am J Health-Syst Pharm. 2010;67(16):1344-1350.
6. Holtorf K. Ur-ine Trouble. Scottsdale, AZ: Vandalay Press; 1998.
7. Woelfel JA. Drug abuse urine tests: false-positive results. Pharmacist's Letter/Prescriber's Letter.
2005;21(3):210314.
Prepared by: Krista Williams, PharmD