Drug Testing - Monitoring of Drugs

  • Diagnosis
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics
  • Videos

Indications for Testing

  • Detection of inappropriate drug use, therapeutic drug monitoring (see Monitoring section), or compliance testing (see Monitoring section)

Laboratory Testing

  • Specimen types
    • Urine
      • Commonly used for compliance testing and to identify inappropriate drug use or exposures
      • Time over which a drug can be detected is drug-specific
      • For more information, refer to the Drug Analytes Detected in Plasma and Urine table
    • Serum/plasma
      • Best specimen to correlate physiological signs and symptoms (eg, impairment, toxicity, therapeutic response) with drug use or concentration
      • Also used when urine is unavailable
      • For most drugs, the specific time over which a drug can be detected is shorter than for urine
      • For more information, refer to the Drug Analytes Detected in Plasma and Urine table
    • Meconium/umbilical cord tissue
    • Hair
      • Long-term exposures
      • Most useful at least one month after a suspected drug exposure or for chronic drug exposures
    • Oral fluid
      • Useful for detection of free drug
      • Represents a time frame of drug use or exposure most similar to serum/plasma
  • Testing approach
    • Drug testing may be performed based on a targeted analysis of one or more drug classes, as in the case of therapeutic drug monitoring or confirmatory testing, or based on a qualitative screen that identifies several drug classes
      • Drug screens can be ordered as “screen only” or with reflex to confirmation
        • Any drug class identified in the screen would be confirmed by a targeted assay
      • Targeted screening and comprehensive screening tests covering a range of drug classes are available
      • Meconium testing is not available as “screen only” due to the high rate of false positive results for some analytes
      • Therapeutic drug monitoring tests are listed at http://www.aruplab.com based on generic name
      • See ARUP Pain Management resource for further information
    • Drug testing may be performed under forensic or non-forensic conditions
      • Forensic
        • Involves a chain of custody
        • Usually performed by a forensic laboratory (eg, blood alcohol testing in an automobile accident or occupational drug testing)
      • Non-forensic
        • Does not involve a chain of custody
        • Usually performed by a clinical laboratory (eg, medical testing)
  • Detection of inappropriate drug use
    • Classic drugs of abuse
      • Five panel drug test [modification of the Substance Abuse and Mental Health Services Administration (SAMHSA) 5] includes the following
        • Amphetamines – amphetamine, methamphetamine, MDMA (ecstasy), MDA, and MDEA
        • Opioids – morphine, codeine, 6-acetylmorphine (heroin metabolite), hydrocodone, hydromorphone, oxycodone, oxymorphone and dihydrocodeine
        • Marijuana metabolite
        • Cocaine metabolite
        • Phencyclidine (PCP)
      • Additional panels include other drug classes
      • Available in urine with or without alcohol testing
    • Extended panels may include the following and are available separately
      • Sedative-hypnotics – benzodiazepines and barbiturates
      • Opioids – buprenorphine, fentanyl, meperidine, methadone, propoxyphene tapentadol, tramadol, and relevant metabolites
      • Stimulants – methylphenidate
      • Tricyclic antidepressants
    • Social drugs, available in extended panels or individually
    • Targeted multi-drug panel for serum/plasma
    • Comprehensive testing for urine or serum/plasma
  • Detection of drugs and the actual concentrations of drugs and drug metabolites depends upon the following
    • Analytical method
      • Cutoff concentrations, sensitivity
      • Drugs included in the test design
      • Specificity
    • Patient
      • Clinical factors (liverkidney, gastrointestinal issues, pregnancy)
      • Age/sex
      • Co-medications
      • Diet
      • Genetic factors
    • Drug of interest
      • Stability in vitro
      • Formulation(s) used
      • Route of administration
      • Pattern of use
      • Pharmacokinetic factors
    • Specimen
      • Timing of specimen collection relative to drug administration
      • Specimen handling/processing
  • Therapeutic drug monitoring
    • Testing to support a wide variety of therapeutic drugs (eg, anticonvulsants, antidepressants, antipsychotics, antiarrhythmics, immunosuppressants) is available; more details are available from the laboratory performing the test
    • Purpose
      • Compare values at steady-state to published therapeutic targets/ranges or individual patient history to optimize dose
        • Examples of drugs for which therapeutic drug monitoring is observed – anti-epileptics, immunosuppressants, anti-arrhythmics, and antibiotics
      • Evaluate clinical signs and symptoms, failure to respond, and toxicity, particularly for drugs with a narrow therapeutic index
      • Detect drug-drug interactions or variation in pharmacokinetics
      • Evaluate compliance with prescribed therapeutic regime
    • Drug testing may include parent drug, free drug, and/or drug metabolites
    • Best specimen
      • Timed blood or serum/plasma
      • Consult laboratory for drug-specific specimen preservatives and handling instructions
    • Time to collect depends on specific drug, patient characteristics, reason for testing
    • Methods may not be equivalent between labs
  • Compliance testing (eg, pain management)
    • Purpose
      • Assure compliance with prescribed (known) drugs
      • Ensure patients are not taking drugs that are not prescribed (licit or illicit)
    • Best specimen
      • Random urine, unless a patient cannot provide a urine specimen (eg, dialysis patient)
      • Diluted urine will compromise detection
    • Drugs detected, cutoffs and approaches vary between labs
      • Consult with laboratory to align needs and requirements with options

Drug testing determines the presence or absence of drugs and/or drug metabolites.  Drug testing may be quantitative (particularly useful for therapeutic drug monitoring) or qualitative to verify compliance with prescribed therapy or identify inappropriate drug use.

Definitions of Drug Testing Terms

Biologic half-life Time required for one-half of a substance (eg, a drug) to be lost through biologic processes (eg, distributed, metabolized, eliminated).
Chain of custody Chronological documentation or paper trail showing the collection, custody, control, transfer, processing, analysis, destruction and disposition of evidence (including biological specimens).
Confirmation test Specific drug test performed after a drug screen to confirm the identity of a drug class, individual parent drug, and/or drug metabolite; confirmatory tests are frequently based on mass spectrometric methods and are often quantitative.
Cutoff Threshold concentration for a drug class, specific drug, or drug metabolite above which a specimen is reported as “positive” or “present”; cutoff may be defined by the manufacturer of a commercial kit (eg, immunoassay) or based on the limit of quantitation validated for a laboratory-developed test (eg, mass spectrometry).
Drug screen Test intended to identify the presence or absence of one or more drug classes or specific drugs.
Free drug Drug or drug metabolite not bound to protein or other moieties such as glucuronides; biological activity, transport, and elimination of drugs and drug metabolites is often different for a free versus a bound drug.
Forensic Relating to or dealing with evidence intended for use in a court of law (eg, to support crime and death investigations, workers’ compensation claims, and pre-employment testing).
Hydrolysis Chemical process of decomposition involving the splitting of a bond and the addition of the hydrogen cation and the hydroxide anion of water.
Common laboratory technique used to dissociate glucuronide and other conjugates of drugs in order to improve detection of many drugs in urine.
Methods that employ hydrolysis prior to analysis are presumed to generate a “total” drug concentration.
Limit of detection (LOD) Concentration at which the target compound can be identified.
Limit of quantification (LOQ) Concentration at which quantitative results can be reported with a high degree of confidence.
Metabolite Any product of metabolism; metabolites can be pharmacologically or toxicologically active or inactive.
Pharmacodynamics Study of drug response, particularly the mechanisms associated with the binding and interactions of pharmacologically active molecules at their tissue site(s) of action.
Pharmacokinetics Study of drug liberation, absorption (bioavailability), distribution, metabolism, and elimination over time.
Specificity Likelihood for detection of a given drug or drug metabolite (ie, likelihood of false-negative and false-positive results).
Total drug Total protein-bound and free drug identified in a specimen; also the concentration resulting after specimen hydrolysis that is thought to represent the sum of free and conjugated drug.

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

Drug screening panels and testing relevant to monitoring pain management patients

Drug tests relevant to all clinical applications

General References

Moeller KE, Lee KC, Kissack JC. Urine drug screening: practical guide for clinicians. Mayo Clin Proc. 2008; 83(1): 66-76. PubMed

Moyer T, McMillin G. Therapeutic Drugs. In Burtis CA, Ashwood ER and Burns DE. Tietz Fundamentals of Clinical Chemistry, 6th ed. MO: Saunders/Elsevier, 2008.

Moyer T, Shaw L. Therapeutic drugs and their management. In Burtis CA, Ashwood ER and Burns DE. Clinical Chemistry & Molecular Diagnositcs, 4th ed. Philadelphia: WB Saunders, 2005.

Porter W. Clinical toxicology. In Burtis CA, Ashwood ER and Burns DE, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics, 7th ed. Philadelphia: WB Saunders, 2014.

Porter W. Clinical Toxicology. In Burtis CA, Ashwood ER and Burns DE. Tietz Fundamentals of Clinical Chemistry, 6th ed. MO: Saunders/Elsevier, 2008.

References from the ARUP Institute for Clinical and Experimental Pathology®

Barakauskas VE, Davis R, Krasowski MD, McMillin GA. Unresolved discrepancies between cannabinoid test results for infant urine. Clin Chem. 2012; 58(9): 1364-7. PubMed

Chittamma A, Marin SJ, Williams JA, Clark C, McMillin GA. Detection of in utero marijuana exposure by GC-MS, ultra-sensitive ELISA and LC-TOF-MS using umbilical cord tissue. J Anal Toxicol. 2013; 37(7): 391-4. PubMed

Johnson-Davis KL, Slawson MH. Ethyl Glucuronide Positivity Rate in a Pain Management Population J Anal Toxicol. 2015; 39(9): 686-90. PubMed

Johnson-Davis KL, Thompson CD, Clark CJ, McMillin GA, Lehman CM. Method comparison of the Ortho Vitros Fusion 5,1 chemistry analyzer and the Roche COBAS Integra 400 for urine drug screen testing in the emergency department. J Anal Toxicol. 2012; 36(5): 345-8. PubMed

Lin C, Nelson GJ, McMillin GA. Evaluation of the NexScreen and DrugCheck Waive RT urine drug detection cups. J Anal Toxicol. 2013; 37(1): 30-6. PubMed

Lin C, Strathmann FG. Elevated urine zinc concentration reduces the detection of methamphetamine, cocaine, THC and opiates in urine by EMIT. J Anal Toxicol. 2013; 37(9): 665-9. PubMed

Marin SJ, Hughes JM, Lawlor BG, Clark CJ, McMillin GA. Rapid screening for 67 drugs and metabolites in serum or plasma by accurate-mass LC-TOF-MS. J Anal Toxicol. 2012; 36(7): 477-86. PubMed

Marin SJ, Roberts M, Wood M, McMillin GA. Sensitive UPLC-MS-MS assay for 21 benzodiazepine drugs and metabolites, zolpidem and zopiclone in serum or plasma. J Anal Toxicol. 2012; 36(7): 472-6. PubMed

Marin SJ, Sawyer JC, He X, Johnson-Davis KL. Comparison of drug detection by three quadrupole time-of-flight mass spectrometry platforms J Anal Toxicol. 2015; 39(2): 89-95. PubMed

McMillin GA, Davis R, Carlisle H, Clark C, Marin SJ, Moody DE. Patterns of free (unconjugated) buprenorphine, norbuprenorphine, and their glucuronides in urine using liquid chromatography-tandem mass spectrometry. J Anal Toxicol. 2012; 36(2): 81-7. PubMed

McMillin GA, Marin SJ, Johnson-Davis KL, Lawlor BG, Strathmann FG. A hybrid approach to urine drug testing using high-resolution mass spectrometry and select immunoassays Am J Clin Pathol. 2015; 143(2): 234-40. PubMed

McMillin GA, Slawson MH, Marin SJ, Johnson-Davis KL. Demystifying analytical approaches for urine drug testing to evaluate medication adherence in chronic pain management. J Pain Palliat Care Pharmacother. 2013; 27(4): 322-39. PubMed

Ward MB, Hackenmueller SA, Strathmann FG, Education Committee of the Academy of Clinical Laboratory Physicians and Scientists. Pathology consultation on urine compliance testing and drug abuse screening. Am J Clin Pathol. 2014; 142(5): 586-93. PubMed

Medical Reviewers

Last Update: June 2016