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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
Author(s) -
Godoy Ana Leonor Pardo Campos,
Parisi Caio Cesar,
Marques Maria Paula,
Coelho Eduardo Barbosa,
Lanchote Vera Lucia
Publication year - 2009
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.20650
Subject(s) - chemistry , chromatography , pharmacokinetics , mexiletine , mass spectrometry , tandem mass spectrometry , enantioselective synthesis , liquid chromatography–mass spectrometry , plasma , pharmacology , organic chemistry , catalysis , medicine , anesthesia , physics , quantum mechanics
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® 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. Chirality, 2009. © 2008 Wiley‐Liss, Inc.