Development of a linear dual column HPLC-MS/MS method and clinical genetic evaluation for tramadol and its phase I and II metabolites in oral fluid
| Autor: | Sooyeun Lee, Chul-Ho Jeong, Hyerim Yu, Seong-Kuk Hong, Jung-Woo Bae |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug Adult Male CYP2D6 media_common.quotation_subject Analgesic Administration Oral digestive system 030226 pharmacology & pharmacy High-performance liquid chromatography 03 medical and health sciences Young Adult 0302 clinical medicine Pharmacokinetics Tandem Mass Spectrometry Drug Discovery medicine Distribution (pharmacology) Humans skin and connective tissue diseases Chromatography High Pressure Liquid Tramadol media_common Chromatography Polymorphism Genetic Chemistry Organic Chemistry Analgesics Opioid Pharmaceutical Solutions 030104 developmental biology Cytochrome P-450 CYP2D6 Molecular Medicine Oral fluid medicine.drug |
| Zdroj: | Archives of pharmacal research. 41(3) |
| ISSN: | 1976-3786 |
| Popis: | Tramadol is a centrally acting synthetic opioid analgesic and has received special attention due to its abuse potential and unexpected responses induced by CYP2D6 polymorphism. Oral fluid is an advantageous biofluid for drug analysis due to non-invasive sampling and high correlation of drug concentrations with plasma. However, few studies have been performed on distribution of tramadol and its metabolites in oral fluid. In the present study, a linear dual column HPLC–MS/MS method was developed and fully validated for the simultaneous determination of tramadol and its phase I [O-desmethyltramadol (ODMT), N-desmethyltramadol (NDMT) and N,O-didesmethyltramadol (NODMT)] and II metabolites in oral fluid. Furthermore, the distribution of tramadol and its metabolites, in relation to CYP2D6 genetic variations, in oral fluid was investigated following a clinical study including 23 subjects with CYP2D6*wt/*wt, CYP2D6*10/*10 or CYP2D6*5/*5. The validation results of selectivity, matrix effect, linearity, precision and accuracy were satisfactory. Pharmacokinetic parameters, such as Css,max and AUC0–τ of tramadol, NDMT and NODMT, in the CYP2D6*10/*10 group were significantly higher than those in the CYP2D6*wt/*wt group. Moreover, the ratios of ODMT/tramadol, NDMT/tramadol and NODMT/NDMT correlated well with the CYP2D6 genotypes. We demonstrated that oral fluid is a promising biofluid for pharmacokinetic evaluation in relation to genetic variations. |
| Databáze: | OpenAIRE |
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