Pre-brief
Urine drug screens (UDS) can be useful tools for critical care providers to determine if a patient is acutely intoxicated or has overdosed on a substance. However, there are pitfalls to using UDS. Many common medications can cross-react with UDS and result in false-positives for substances of abuse. This can lead to serious medical and social consequences including unnecessary medical treatment and mistrust. Knowledge of medications that could potentially cross-react with UDS is essential.
Why urine samples and not blood samples?
Urine is the preferred means of drug screen collection because concentrations of drugs and their metabolites are high in the urine. Furthermore, drugs captured in urine have longer detection times than drugs captured in serum. Urine specimens collected in the morning are the most reliable because they are the most concentrated.

Immunoassay vs gas chromatography-mass spectrometry (GC-MS) – which is a better test?
An immunoassay is the most common method of performing UDS due to its simplicity, low cost, and prompt delivery of results. Unfortunately, immunoassays are prone to errors due to cross-reactivity from structurally related and unrelated compounds. Results of immunoassays should always be considered “presumptive” until confirmed by GC-MS which is the most accurate, sensitive, and reliable method of testing. Unfortunately, GC-MS is time-consuming, expensive, and requires a high level of expertise to perform. Most hospitals lack GC-MS testing.

What about false-negatives?
False-negatives do exist and can be caused by a variety of factors such as cross-reactivity of the antibody used by the immunoassay, the cutoff concentration for a positive result (ex: concentration of the substance in the urine may be below the prespecified cutoff value resulting in a false-negative), or an extended length of time passing between substance ingestion and acquisition of the urine sample.
Limitations of UDS:
UDS do not provide information about the length of time since the last ingestion nor do they provide information about the duration of ingestion if long term. The components of a UDS may also differ from institution to institution; if a patient has a negative UDS, they still may have ingested a substance not tested for.
The Debrief
- Obtain a urine sample earlier rather than later if an intoxication/overdose is suspected to minimize the chance of a false-negative result.
- If obtainable, record a detailed medication history including prescriptions, over-the-counter medications, herbal remedies, or any illicit drugs the patient is taking.
- If you feel there is an immunoassay UDS with questionable results, ask to have a GC-MS test done if it is available at your institution. If GC-MS is not available, review the patient’s medication list to see if there are any medications that could potentially cross-react with the immunoassay and cause a false-positive result.
References
- Moeller K, Lee K, Kissack J. Urine Drug Screening: Practical Guide for Clinicians. Mayo Clin Proc. 2008; 83(1)66-76.
- Kronstrand R, Nystrom I, Andersson M, et al. Urinary Detection Times and Metabolite/Parent Compound Ratios After a Single Dose of Buprenorphine. J Anal Toxicol. 2008; 32 (586-93).
- Saitman A, Park H, Fitzgerald R. False-Positive Interferences of Common Urine Drug Screen Immunoassays: A Review. J Anal Toxicol. 2014; 38(7)387-96.
- Brahm N, Yeager L, Fox M, et al. Commonly Prescribed Medications and Potential False-Positive Urine Drug Screens. Am J Health-Syst Pharm. 2010; 67:1344-50.
don’t forget that the test being used by YOUR hospital/test center may or may not test for the substance you are looking for. Not all assays are the same. And none of the specimens are collected with a chain of custody so none of them can “be used against” a patient (for some sick, vindictive reason this comes up on rounds more often than I care to admit).