Modification of screening immunoassays to detect sub-threshold concentrations of cocaine, cannabinoids, and opiates in urine: Use for detecting maternal and neonatal drug exposures

Testing for drugs of abuse in urine is commonplace in emergency departments and neonatal units. However, the clinical sensitivity of immunochemical sc reening methods is limited by the threshold concentrations used to distingu ish between positive and negative specimens. Immunochemical screening metho ds for cocaine metabolite (benzoylecgonine), cannabinoids, and opiates in u rine were recalibrated to detect drugs at lower threshold concentrations. T he precision and linearity of the signals at the modified thresholds were v erified by diluting drug-positive urine specimens to concentrations below t he conventional cutoff concentration and measuring the rate signals in trip licate. To assess the clinical performance of the modified methods, specime ns that tested negative using the unmodified assays were re-screened at the lower threshold, and specimens that rescreened positive were submitted for gas chromatographic/mass spectrometric (GC/MS) confirmation. Reproducibili ty of sub-threshold measurements was comparable to the unmodified assays, a nd rate separations between successive dilutions were sufficient to give se mi-quantitative results. Using the lower thresholds, drugs were detected in 4-5% of the subjects that had screened negative at the conventional thresh old concentration. GC/MS analysis confirmed the presence of cannabinoids an d cocaine metabolite in 74% and 84%, respectively, of urine specimens that re-screened positive. Morphine, codeine, hydromorphone, or hydrocodone was detected by GC/MS analysis in 31% of opiate-positive re-screens.