Department of Family and Community Medicine, Medical College of Wisconsin, Milwaukee (Dr. Hayes); Waukesha Family Medicine Residency at ProHealth Care, WI (Dr. Fox) jrhayes@mcw.edu
The authors reported no potential conflict of interest relevant to this article.
Interference falls into 2 categories: variables inherent in the testing process and patient variables.
Obtain consent prior to performing urine drug screening, even if you are already collecting a specimen for other testing.
Antibody cross-reactivity. A major disadvantage of immunoassay technology is interference that results in false-positive and false-negative results.19,20 The source of this interference is antibody cross-reactivity—the degree to which an antibody binds to structurally similar compounds. Antibody–antigen interactions are incredibly complex; although assay antibodies are engineered to specifically detect a drug class of interest, reactivity with other, structurally similar compounds is unavoidable.
Nevertheless, cross-reactivity is a useful phenomenon that allows broad testing for multiple drugs within a class. For example, most point-of-care tests for benzodiazepines reliably detect diazepam and chlordiazepoxide. Likewise, opiate tests reliably detect natural opiates, such as morphine and codeine. Cross-reactivity is not limitless, however; most benzodiazepine immunoassays have poor reactivity to clonazepam and lorazepam, making it possible that a patient taking clonazepam tests negative for benzodiazepine on an immunoassay.14,20 Similarly, standard opioid tests have only moderate cross-reactivity for semisynthetic opioids, such as hydrocodone and hydromorphone; poor cross-reactivity for oxycodone and oxymorphone; and essentially no cross-reactivity for full synthetics, such as fentanyl and methadone.14
It is the responsibility of the ordering physician to understand cross-reactivity to various drugs within a testing class.
Routine urine drug screening at every visit can make urine tampering more likely and is often unnecessary for stable patients.
Whereas weak cross-reactivity to drugs within a class can be a source of false-negative results, cross-reactivity to drugs outside the class of interest is a source of false-positive results. An extensive review of drugs that cause false-positive immunoassay screening tests is outside the scope of this article; commonly prescribed medications implicated in false-positive results are listed in TABLE 1.19
