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.
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.
Godoy
Ana Leonor Pardo Campos
AL
Department of Clinical, Toxicologic and Bromatologic Analyses, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Parisi
Caio Cesar
CC
Marques
Maria Paula
MP
Coelho
Eduardo Barbosa
EB
Lanchote
Vera Lucia
VL
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*
D000889:Anti-Arrhythmia Agents; D003470:Culture Media; D004365:Drugs, Chinese Herbal; D008801:Mexiletine; C045807:6-hydroxymethylmexiletine; C045808:4-hydroxymexiletine