Enantioselective determination of mexiletine and its metabolites p-hydroxymexiletine and hydroxymethylmexiletine in rat plasma by normal-phase liquid chromatography-tandem mass spectrometry: application to pharmacokinetics |
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| Authors: | Godoy Ana Leonor Pardo Campos Parisi Caio Cesar Marques Maria Paula Coelho Eduardo Barbosa Lanchote Vera Lucia |
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| Institution: | 1. Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeir?o Preto, University of S?o Paulo, Ribeir?o Preto, SP, Brazil;2. Department of Internal Medicine, Discipline of Nephrology, Faculty of Medicine of Ribeir?o Preto, University of S?o Paulo, Ribeir?o Preto, SP, Brazil |
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| Abstract: | Mexiletine (MEX), hydroxymethylmexiletine (HMM) and p-hydroxymexiletine (PHM) were analyzed in rat plasma by LC-MS/MS. The plasma samples were prepared by liquid-liquid extraction using methyl-tert-butyl ether as extracting solvent. MEX, HMM, and PHM enantiomers were resolved on a Chiralpak(R) AD column. Validation of the method showed a relative standard deviation (precision) and relative errors (accuracy) of less than 15% for all analytes studied. Quantification limits were 0.5 ng ml(-1) for the MEX and 0.2 ng ml(-1) for the HMM and PHM enantiomers. The validated method was successfully applied to quantify the enantiomers of MEX and its metabolites in plasma samples of rats (n = 6) treated with a single oral dose of racemic MEX. |
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| Keywords: | mexiletine metabolism enantiomers pharmacokinetics rats LC‐MS‐MS |
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