Simultaneous Determination of Ketamine, Tramadol, Methadone, and their Metabolites in Urine by Gas Chromatography-Mass Spectrometry

An automated solid-phase extraction procedure combined with gas chromatography-mass spectrometry methodology, without derivatization, has been developed for the identification and quantitation of ketamine, norketamine, tramadol, methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine, and 2-ethyl-5-methyl-3,3-diphenylpyrroline in urine. The analytical approach is simple and rapid, yet reliable. Good linearity (r(2) > 0.995 over the concentration range of 30 to 600 ng/mL), sensitivity (limits of quantitation 15-30 ng/mL), accuracy (81.0-109.9%), precision (RSD < 13.8%), and recovery (> 79.6% in average) were achieved for all analytes. Ninety-one urine specimens from suspected drug users and 21 clinical urine specimens from methadone substitution therapy patients were analyzed to validate the method compatibility and stability. Results have demonstrated that this GC-MS method is a good confirmation and quantitation test scheme for the six target compounds in urine.