Protocol - Lab-based Urine Drug Analysis
Protocol Name from Source:This section will be completed when reviewed by an Expert Review Panel.
Description:A urine specimen is collected from the participant and tested to detect recent drug use. Urine tests may be used to detect cannabis, cocaine, amphetamines, opiates (heroin, codeine, or morphine), methamphetamines, or buprenorphine use. Multiple tests may be used on aliquots of the same urine sample. Screening involves an enzyme immunoassay targeting the drug or its metabolites. Confirmation of a positive screening result involves gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis targeting the drug or its metabolites. Nearly all the drugs have a drug detection window for the assay performed. The detection window is the amount of time a particular amount of the drug can be in the body and detected by the assay. The drug detection window listed subsequently is an estimate; the actual detection time will vary by the amount and frequency of drug taken and individual variability in rates of drug metabolism and elimination. Some tests are available with different cut-off concentrations. In general, lower cut-off concentrations give longer detection windows, and higher cut-off concentrations give shorter detection windows. The cut-off concentrations listed below are those recommended by the Substance Abuse and Mental Health Services Administration (SAMSHA) for workplace testing. The concentrations used in clinical trials may differ; for example, the concentrations typically used in trials of cocaine and opiate dependence treatment are 300 ng/ml for cocaine metabolites and 300 ng/ml for morphine, respectively.
Urine collection, processing, and storage
The participant is asked to urinate into a sterile 90 ml urine specimen container. Specimen collection should be observed to prevent specimen adulteration or substitution. Specimens should be refrigerated immediately after collection and aliquoted into a 4 ml cryovial (for each drug type being tested) within 48 hours. Cryovials should be frozen at -20˚C until analysis. Specimens should be analyzed within 2 months of collection.
Enzyme immunoassay should be employed to detect the marijuana metabolite Δ9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH). The assay will reliably detect marijuana metabolite concentrations greater than 50 ng/ml.
Gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis should be employed to accurately detect THCCOOH concentrations greater than 15 ng/ml.
Cannabis detection window
a) It has been reported that after occasional use, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (THCCOOH) concentrations in urine remain above 15 ng/ml after alkaline hydrolysis for up to 4 days (Huestis et al., 1996).
b) Urinary THCCOOH detection windows range from several days in infrequent users to months in frequent users (Ellis et al., 1985; Peat, 1989; Kelly & Jones, 1992; Fraser & Worth, 2003; Lowe et al., 2009).
c) Differentiating new cannabis use from prolonged urinary excretion in chronic users is difficult. Several mathematical approaches for identifying new cannabis use based upon creatinine corrected THCCOOH urinary concentrations have been reported (Huestis et al., 1998; Schwilke et al., 2011; Smith et al., 2009).
d) Research continues to identify biomarkers for directly distinguishing new cannabis use (Skopp & Potsch, 2002; Mareck et al., 2009; Weinmann et al., 2000).
Enzyme immunoassay should be employed to detect the cocaine metabolite benzoylecgonine (BE). The assay will reliably detect cocaine metabolite concentrations greater than 300 ng/ml.
Gas chromatographic mass spectrometric (GCMS) or liquid chromatographic mass spectrometric analysis should be employed to accurately detect BE concentrations greater than 150 ng/ml.
Cocaine detection window
The Drugs of Abuse Reference Guide indicates the urine screening cutoff for cocaine detection is 300 ng/ml. National Institute of Drug Abuse (NIDA) clinical trials also use this concentration as the threshold. GCMS can confirm a concentration of 150 ng/ml or greater. The urine detection time is 2–5 days (Lab Corporation of America, 2007).
Amphetamine or methamphetamine
Enzyme immunoassay should be employed to reliably detect methamphetamine concentrations greater than 500 ng/ml.
Gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis should be employed to accurately detect methamphetamine concentrations greater than 250 ng/ml and amphetamine concentrations greater than 100 ng/ml. To be positive for methamphetamine, a specimen must exceed 250 ng/ml methamphetamine and contain more than 100 ng/ml of amphetamine.
Methamphetamine detection window
25–77 hrs after oral administration of a single 10 mg methamphetamine hydrochloride sustained release capsule methamphetamine and amphetamine urine concentrations exceeded 250 and 100 ng/ml, respectively (n = 5) (Oyler et al., 2002).
Enzyme immunoassay should be employed to reliably detect morphine concentrations greater than 300 ng/ml.
Gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis should be employed to accurately detect codeine and morphine concentrations greater than 300 ng/ml.
Opiate detection window
The Drugs of Abuse Reference Guide indicates the urine screening cutoff for codeine and morphine detection is 300 ng/ml. National Institute of Drug Abuse (NIDA) clinical trials also use this concentration as the threshold. GCMS can confirm a concentration of 300 ng/ml or greater. The urine detection time is 2–3 days (Lab Corporation of America, 2007).
Methylenedioxymethamphetamine (MDMA, ecstasy), methylenedioxyamphetamine (MDA) or methylenedioxyethylamphetamine (MDEA)
Enzyme immunoassay should be employed to reliably detect MDMA concentrations greater than 500 ng/ml.
Gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis should be employed to accurately detect MDMA, MDA, and MDEA concentrations greater than 250 ng/ml.
MDMA detection window
Following a single 1.0 or 1.6 mg/kg oral administration of MDMA, urine specimens were unlikely to contain more than 250 ng/ml of MDMA for more than 48 hrs after dosing (n = 16) (Abraham et al., 2009).
Enzyme immunoassay should be employed to reliably detect methadone concentrations greater than 300 ng/ml.
Gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis should be employed to accurately detect methadone and 2-ethylidine-1,5dimethyl-3,3-diphenylpyrrolidine (EDDP) concentrations greater than 100 ng/ml.
Enzyme immunoassay should be employed to reliably detect norbuprenorphine, the metabolite of buprenorphine, at levels greater than 10 ng/ml.
Gas chromatographic mass spectrometric or liquid chromatographic mass spectrometric analysis should be employed to accurately detect buprenorphine at levels greater than 2 ng/ml.
Interpretation of Results
In general, a positive result, i.e., the presence of drug is detected in an enzyme immunoassay, indicates that the individual has ingested the drug, or a drug in the same chemical class, within the window of detection. Not all positive drug screens are due to illicit drug use or are confirmed. Drugs taken in low doses or at times outside of the window of detection may not result in a positive drug screen.
Personnel and Training Required
Urine collection supervised by a same-sex observer is required.
A laboratory capable of performing the specific enzyme immunoassay, gas chromatographic mass spectrometry, or liquid chromatographic mass spectrometry
Standard sterile urine collection supplies
Biological specimens may be shipped via appropriate procedures to laboratories specializing in urine analysis.
|Average time of greater than 15 minutes in an unaffected individual||No|
|Specialized requirements for biospecimen collection||No|
Mode of Administration
Collected by Study Staff
Adolescent, Adult, Senior
Testing must be performed by a laboratory that is certified by the College of American Pathologists or that follows Good Laboratory Practice. Laboratory methods vary. Investigators should contact their laboratory for specific instructions on specimen collection, handling, and storage. Investigators should also check with their laboratory about concentration cutoffs for positive tests and the sensitivity, specificity, and cross-reactivity of the enzyme immunoassay used by the laboratory.
The Substance Abuse and Addiction Working Group acknowledges that the following questions may gather sensitive information relating to the use of substances and/or illegal conduct. If the information is released, it might be damaging to an individual's employability, lead to social stigmatization, or lead to other consequences.
Most researchers assure confidentiality as part of their informed consent process, as required by their institutional review boards. When assessing minors with these questions, it may be necessary to obtain informed consent from a parent of the adolescent. Further assurance of confidentiality may be obtained by applying to the National Institutes of Health (NIH) for a Certificate of Confidentiality, which helps researchers protect the privacy of human research participants. The procedures for the Certificate of Confidentiality can be found at the Grants Policy website of the NIH: http://grants1.nih.gov/grants/policy/coc/index.htm.
February 24, 2012
DefinitionBioassay used to detect and quantify recent illegal drug use.
This assay is used to detect whether or not the participant has recently used an illegal drug or multiple illegal drugs. It is a quantitative assay that can be used to measure drug concentrations in urine.
Enzyme immunoassay urine screening is commonly used for detecting cannabis, cocaine, amphetamine, opiate, methamphetamine, or buprenorphine use. This type of assay is preferred because of nonintensive specimen preparation and ease of instrument operation. For some applications, screening tests may be adequate.
Enzyme immunoassay urine screening cannot be used to accurately measure drug concentrations. Gas chromatography or liquid chromatography mass spectrometric methodology must be employed to accurately measure drug/drug metabolite concentrations in urine.
|Common Data Elements (CDE)||Drug Abuse Urine Laboratory Test Positive Negative Code||3332430||CDE Browser|
Process and Review
This section will be completed when reviewed by an Expert Review Panel.
Department of Health and Human Services, Substance Abuse and Mental Health Services Administration. (2008). Mandatory guidelines for federal workplace drug testing programs; Notice. Federal Register, 73(228), 71858–71907.
Abraham, T., Barnes, A., Lowe, R., Kolbrich Spargo, E. A., Milman, G., Pirnay, S., Gorelick, D., Goodwin, R., & Huestis, M. (2009). Urinary MDMA, MDA, HMMA, and HMA excretion following controlled MDMA administration to humans. Journal of Analytical Toxicology, 33(8), 439–446.
Ellis, G. M., Mann, M. A., Judson, B. A., Schramm, N. T., & Tashchian, A. (1985). Excretion patterns of cannabinoid metabolites after last use in a group of chronic users. Clinical Pharmacology and Therapeutics, 38(5), 572–578.
Fraser, A. D., & Worth, D. (2003). Urinary excretion profiles of 11-nor-9-carboxy-Delta9-tetrahydrocannabinol. Study III. A Delta9-THC-COOH to creatinine ratio study. Forensic Science International, 137(2–3), 196–202.
Huestis, M. A., & Cone, E. J. (1998). Differentiating new marijuana use from residual drug excretion in occasional marijuana users. Journal of Analytical Toxicology, 22(6), 445–454.
Huestis, M. A., Mitchell, J. M., & Cone, E. J. (1996). Urinary excretion profiles of 11-nor-9-carboxy-9-tetrahydrocannabinol in humans after single smoked doses of marijuana. Journal of Analytical Toxicology, 20(6), 441–452.
Kelly, P., & Jones, R. T. (1992). Metabolism of tetrahydrocannabinol in frequent and infrequent marijuana users. Journal of Analytical Toxicology, 16(4), 228–235.
Lab Corporation of America. (2007). Drugs of abuse reference guide. Retrieved from https://www.labcorpsolutions.com/images/Drugs_of_Abuse_Reference_Guide_Flyer_3166.pdf
Lowe, R., Abraham, T., Darwin, W., Herning, R., Cadet, J., & Huestis, M. (2009). Extended urinary delta 9 tetrahydrocannabinol excretion in chronic cannabis users precludes use as a biomarker of new drug exposure. Drug and Alcohol Dependence, 105(1–2), 24–32.
Mareck, U., Haenelt, N., Geyer, H., Guddat, S., Kamber, M., Brenneisen, R., Thevis, M., & Sch¿er, W. (2009). Temporal indication of cannabis use by means of THC glucuronide determination. Drug Testing and Analysis, 1(11–12), 505–510.
Oyler, J. M., Cone, E. J., Joseph, R. E., Jr., Moolchan, E. T., & Huestis, M. A. (2002). Duration of detectable methamphetamine and amphetamine excretion in urine after controlled oral administration of methamphetamine to humans. Clinical Chemistry, 48(10), 1703–1714.
Peat, M. A. (1989). Distribution of delta-9-tetrahydrocannabinol and its metabolites. In R. C. Baselt (Ed.), Advances in analytic toxicology II (pp. 186–217). Chicago, IL: Book Medical Publishers.
Schwilke, E. W., Gullberg, R. G., Darwin, W. D., Chiang, C. N., Cadet, J. L., Gorelick, D. A., Pope, H. G., & Huestis, M. A. (2011). Differentiating new cannabis use from residual urinary cannabinoid excretion in chronic, daily cannabis users. Addiction, 106(3), 499–506.
Skopp, G., & Potsch, L. (2002). Stability of 11-nor-delta(9)-carboxy-tetrahydrocannabinol glucuronide in plasma and urine assessed by liquid chromatography-tandem mass spectrometry. Clinical Chemistry, 48(2), 301–306.
Smith, M. L., Barnes, A. J., & Huestis, M. A. (2009). Identifying new cannabis use with urine creatinine-normalized THCCOOH concentrations and time intervals between specimen collections. Journal of Analytical Toxicology, 33(4), 185–189.
Weinmann, W., Vogt, S., Goerke, R., Muller, C., & Bromberger, A. (2000). Simultaneous determination of THC-COOH and THC-COOH-glucuronide in urine samples by LC/MS/MS. Forensic Science International, 113(1–3), 381–387.
|Variable Name||Variable ID||Variable Description||Version||dbGaP Mapping|
|PX510701_MDMA_Ecstasy||PX510701060000||Methylenedioxymethamphetamine (MDMA, ecstasy), methylenedioxyamphetamine (MDA) or methylenedioxyethylamphetamine (MDEA)||4||N/A|