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 b2;-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.