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Strategies for preventing and detecting false-negatives in urine drug screens

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Urine drug screening (UDS) is an important tool in emergency settings and substance abuse or pain management clinics. According to the 2015 National Survey on Drug Use and Health, 9.2% of individuals age ≥12 used an illicit drug other than marijuana within the previous year.1

There are 2 types of UDS: gas chromatography–mass spectroscopy (GC-MS) and enzymatic immunoassay (EIA). A GC-MS uses a 2-step mechanisms to detect chemical compounds. First the GC separate the illicit substance into molecules, which is then introduced to the MS, which then separates compounds depending on their mass and charge using magnetic fields.2,3 Although GC-MS is a more definitive means to confirm the presence of a specific drug, it rarely is used in clinical settings because it is expensive and time-consuming.

EIA is an anti-drug antibody added to the patient’s urine that causes a positive indicator reaction that can be measured.2,3 It is a rapid, accurate, and cost-effective way of detecting illicit substances.4 However, there are limitations to EIAs used in most hospital laboratories.

Limitations of EIAs

Timing. Results of the drug screen depend on the time and frequency of drug use (Table 1).5



Sensitivity. The immunoassay methods used vary in their ability to detect substances and depend on the test’s sensitivity; however, most of these versions have high sensitivity for detecting many illicit substances.4

Specificity and cross-reactivity. Unfortunately, many drugs, such as opioids, amphetamines, and commonly prescribed medications, exhibit cross-reactivity that can produce false-positive results (Table 2).5,6



Synthetic cannabinoids, such as “spice” and cathinones, also known as “bath salts,” cannot be detected with standard UDS. However, some newer EIA kits can detect synthetic cannabinoids but do not detect newer designer drugs.7 Detection of specific cathinones by EIA is not yet available.7

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