Savvy Psychopharmacology

Urine drug screens: When might a test result be false-positive?

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Mr. L, age 35, has an appointment at a mental health clinic for ongo­ing treatment of depression. His medication list includes atorvastatin, bupro­pion, lisinopril, and cranberry capsules for non-descriptive urinary issues. He has been treated for some time at a different outpa­tient facility; however he recently moved and changed clinics.

At this visit, his first, Mr. L receives a full physical exam, including a urine drug screen point-of-care (POC) test. He informs the nurse that he has an extensive history of drug abuse: “You name it, I’ve done it.” Although he experimented with many illicit substances, he acknowledges that “down­ers” were his favorite. He believes that his drug abuse could have caused his depres­sion, but is proud to declare that he has been “clean” for 12 months and his depression is approaching remission.

However, the urine drug screen is positive for amphetamines. Mr. L vehemently swears that the test must be wrong, restating that he has been clean for 12 months. “Besides, I don’t even like ‘uppers’!” Because of Mr. L’s insistence, the clinician does a brief literature search about false-positive results in urine drug screening, which shows that, rarely, bupropion can trigger a false positive in the amphetamine immunoassay.

Could this be a false-positive result? Or is Mr. L not telling the truth?

Because no clinical lab test is perfect, any clinician who runs urine drug screens will encounter a false-positive result. (See the Box,1-3 for discussion of false negatives.) Understanding how each test works—and potential sources of error— can help you evaluate test results and determine the best course of action.

There are 2 main methods involved in urine drug testing: in-office (POC) urine testing and laboratory-based testing. This article describes the differences between these tests and summarizes the potential for false-positive results.

In-office urine testing
POC tests in urine drug screens use a tech­nique called “immunoassay,” which is quantitative and generally will detect the agent in urine for only 3 to 7 days after ingestion.4 This test relies on the principle of competitive binding: If a parent drug or metabolite is present in urine, it will bind to a specific antibody site on the test strip and produce a positive result.5 Other compounds that are similarly “shaped” on a molecular level also can bind to these antibody sites when present in sufficient quantity, producing a “cross reaction,” also called a “false-positive” result. The Table6 lists agents that can cross-react with immu­noassay tests. In addition to the cross-reaction, false positives also can occur because of technician or clerical error— making it important to review the process by which the specimen was obtained and tested if a false-positive result is suspected, as in the case described here.7


Different POC tests can have vary­ing cross-reactivity patterns, based on the antibody used.8 In general, false positives in immunoassays are rare, but amphetamine and opiate false posi­tives are more common than cocaine metabolite and cannabinoid false posi­tives.9 The odds of a false positive vary, depending on the specificity of the immunoassay used and the substance under detection.6

A study that analyzed 10,000 POC urine drug screens found that 362 speci­mens tested positive for amphetamines, but that 128 of those did not test posi­tive for amphetamines using more sensitive tests.10 Of these 128 false posi­tives reported, 53 patients were tak­ing bupropion at the time of the test.10 Therefore, clinicians should do a thor­ough patient medication review at the time of POC urine drug testing. In addi­tion, consider identifying which type of test you are using at your practice site, and ask the manufacturer or lab to provide a list of known possible false positives.

Laboratory-based GC–MS testing
If a false positive is suspected on a POC immunoassay-based urine drug screen, results can be confirmed using gas chromatography–mass spectrometry (GC–MS). Although GC–MS is more accu­rate than an immunoassay, it also is more expensive and time-consuming.9

GC–MS breaks down a specimen into ionized fragments and separates them based on their mass–charge ratio. Because of this, GC–MS is able to identify the presence of a specific drug (eg, oxyco­done) instead of a broad class (eg, opi­oid). The GC–MS method is a good tool to confirm initial positive screens when their integrity is in question because, unlike POC tests used during an office visit, GC–MS is not influenced by cross-reacting compounds.11-13

GC–MS is not error-free, however. For example, heroin and hydrocodone are metabolized into morphine and hydro­morphone, respectively. Depending on when the specimen was collected, the metabolites, not the parents, might be the compounds identified, which might pro­duce confusing results.

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