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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
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
- Source :
- Archives of pharmacal research. 41(3)
- Publication Year :
- 2017
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 19763786
- Volume :
- 41
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Archives of pharmacal research
- Accession number :
- edsair.doi.dedup.....28e84e7bf778264931a0dcc315049a53