Urine testing for norcodeine, norhydrocodone, and noroxycodone facilitates interpretation and reduces false negatives

Urine drug testing of pain patients provides objective information to health specialists regarding patient compliance, diversion, and concurrent illicit drug use. Interpretation of urine test results for semi-synthetic opiates can be difficult because of complex biotransformations of parent drug to metabolites that are also available commercially and may be abused. Normetabolites such as norcodeine, norhydrocodone and noroxycodone are unique metabolites that are not available commercially. Consequently, detection of normetabolite in specimens not containing parent drug, provides conclusive evidence that the parent drug was consumed.The goal of this study was to evaluate the prevalence and patterns of the three normetabolites, norcodeine, norhydrocodone and noroxycodone, in urine specimens of pain patients treated with opiates. Urine specimens were hydrolyzed with β-glucuronidase and analyzed by a validated liquid chromatography tandem mass spectrometry (LC/MS/MS) assay for the presence of codeine, norcodeine, morphine, hydrocodone, norhydrocodone, hydromorphone, dihydrocodeine, oxycodone, noroxycodone, and oxymorphone. The limit of quantitation (LOQ) for these analytes was 50. ng/mL. The study was approved by an Institutional Review Board.Of the total specimens (N=2654) tested, 71.4% (N=1895) were positive (≥LOQ) for one or more of the analytes. The prevalence (%) of positive results for codeine, hydrocodone and oxycodone was 1.2%, 26.1%, and 36.2%, respectively, and the prevalence of norcodeine, norhydrocodone and noroxycodone was 0.5%, 22.1%, and 31.3%, respectively. For specimens containing normetabolite, the prevalence of norcodeine, norhydrocodone and noroxycodone in the absence of parent drug was 8.6%, 7.8% and 9.4%, respectively. From one-third to two-thirds of these specimens also did not contain other metabolites that could have originated from the parent drug. Consequently, the authors conclude that inclusion of norcodeine, norhydrocodone and noroxycodone is useful in interpretation of opiate drug source and reduces potential false negatives that would occur without tests for these unique metabolites.