title: 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.
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.
authors.affiliation: Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Ana Leonor Pardo Campos
authors.initials: AL
authors.lastname: Godoy
authors.forename: Caio Cesar
authors.initials: CC
authors.lastname: Parisi
authors.forename: Maria Paula
authors.initials: MP
authors.lastname: Marques
authors.forename: Eduardo Barbosa
authors.initials: EB
authors.lastname: Coelho
authors.forename: Vera Lucia
authors.initials: VL
authors.lastname: Lanchote
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002853:Chromatography, Liquid; D003470:Culture Media; D004365:Drugs, Chinese Herbal / Q000032:analysis; D008297:Male; D013058:Mass Spectrometry; D008801:Mexiletine / Q000031:analogs & derivatives* / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D000889:Anti-Arrhythmia Agents; D003470:Culture Media; D004365:Drugs, Chinese Herbal; D008801:Mexiletine; C045807:6-hydroxymethylmexiletine; C045808:4-hydroxymexiletine