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- W2023745848 abstract "Abstract Tramadol (T) is available as a racemic mixture of (+)‐ trans ‐T and (−)‐ trans ‐T. The main metabolic pathways are O‐demethylation and N‐demethylation, producing trans ‐O‐desmethyltramadol ( M1 ) and trans ‐N‐desmethyltramadol ( M2 ) enantiomers, respectively. The analgesic effect of T is related to the opioid activity of (+)‐ trans‐ T and (+)‐ M1 and to the monoaminergic action of (+/−)‐ trans ‐T. This is the first study using tandem mass spectrometry as a detection system for the simultaneous analysis of trans ‐T, M1 , and M2 enantiomers. The analytes were resolved on a Chiralpak® AD column using hexane:ethanol (95.5:4.5, v/v) plus 0.1% diethylamine as the mobile phase. The quantitation limits were 0.5 ng/ml for trans‐ T and M1 and 0.1 ng/ml for M2 . The method developed and validated here was applied to a pharmacokinetic study in rats. Male Wistar rats ( n = 6 at each time point) received a single oral dose of 20 mg/kg racemic trans ‐T. Blood samples were collected up to 12 h after drug administration. The kinetic disposition of trans‐ T and M2 was enantioselective (AUC (+)/( −) ratio = 4.16 and 6.36, respectively). The direction and extent of enantioselectivity in the pharmacokinetics of trans ‐T and M2 in rats were comparable to data previously reported for healthy volunteers, suggesting that rats are a suitable model for enantioselective studies of trans ‐T pharmacokinetics. Chirality, 2011. © 2010 Wiley‐Liss, Inc." @default.
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- W2023745848 date "2010-11-29" @default.
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- W2023745848 title "Simultaneous analysis of tramadol, O-desmethyltramadol, and N-desmethyltramadol enantiomers in rat plasma by high-performance liquid chromatography-tandem mass spectrometry: Application to pharmacokinetics" @default.
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- W2023745848 doi "https://doi.org/10.1002/chir.20914" @default.
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