Development of a column-switching LC-MS/MS method of tramadol and its metabolites in hair and application to a pharmacogenetic study
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Hair is a valuable specimen for monitoring long-term drug use. Tramadol is an effective opioid analgesic but is associated with risks such as drug dependence and unexpected toxicity arising from genetic differences in metabolism. However, few studies have been performed on the distribution of tramadol and its metabolites in hair. In the present study, a column-switching LC-MS/MS method was developed and fully validated for the simultaneous determination of tramadol and its phase I and II metabolites in hair. Furthermore, the distribution of tramadol and its metabolites in hair was investigated in a pharmacogenetic study. Tramadol and its metabolites were extracted from hair using methanol and injected onto LC-MS/MS. The validation results of selectivity, matrix effect, linearity, precision and accuracy were satisfactory. The (mean) concentrations of O-desmethyltramadol (ODMT) and N,O-didesmethyltramadol (NODMT) in the CYP2D6*10/*10 and CYP2D6*5/*5 groups were lower than those in the CYP2D6*wt/*wt group, while the (mean) concentrations of N-desmethyltramadol (NDMT) were higher. Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT were well correlated with the CYP2D6 genotypes. The developed method was successfully applied to the clinical study, which demonstrated that the concentrations of a drug and its metabolites in hair were dependent on the polymorphism of its metabolizing enzyme.
KeywordsDrug abuse Tramadol Hair analysis LC-MS/MS CYP2D6 Genetic polymorphism
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning (NRF-2015M3A9E1028327) and by the Basic Science Research Program of NRF funded by the Ministry of Education (NRF-2016R1A6A1A03011325).
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Conflict of interest
The authors declare that they have no conflict of interest.
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