Direct-to-definitive urine drug screening in children unmasks false-negative immunoassay screening

Routine urine drug screening is performed using immunoassays. False-positive immunoassay results are well documented and confirmatory testing is essential. False-negative rates have not been rigorously quantified. Our study estimates the false-negative rate of immunoassay screening in a pediatric population.

Drug screening in the St. Louis Children's laboratory employs a broad spectrum direct to LC-MS/MS approach. We selected 125 urine specimens over five months (4% of 3000 screens), that were weakly positive for amphetamines, benzoylecgonine, THC, opiates, fentanyl, benzodiazepines, and methadone using LC-MS/MS. These specimens were reanalyzed by immunoassay on a Roche Cobas platform (forward approach). Second, we collected 145 negative urine specimens from five pediatric settings using immunoassay platforms including Viva-ProE (Siemens), Vitros (Ortho), Atellica (Siemens) and Cobas (Roche). These specimens were subjected to our local LC-MS/MS analysis (reverse approach).

Among the 125 LC-MS/MS positive samples, 112 (90%) contained at least one substance that was targeted but not detected by immunoassay. The most frequently missed substances were methamphetamine and benzoylecgonine. Among the 145 negative urine specimens from routine immunoassay, LC-MS/MS identified substances in 16 (11%) that were targeted and missed by immunoassay and identified substances in 34 (23%) that were not covered by immunoassay.

Our study indicates that 4-11% of pediatric urine specimens contain substances targeted and missed by conventional immunoassays. Another quarter may contain substances not covered by immunoassay. These false negatives can lead to the discharge of a child into an unsafe environment. Direct to LC-MS/MS screening acts to minimize false-negative immunoassay drug screens.