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

Chirality. 2009 Jul;21(7):648-56. doi: 10.1002/chir.20650.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Arrhythmia Agents
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, Liquid
  • Culture Media
  • Drugs, Chinese Herbal / analysis
  • Male
  • Mass Spectrometry
  • Mexiletine / analogs & derivatives*
  • Mexiletine / analysis
  • Mexiletine / metabolism
  • Rats
  • Rats, Wistar
  • Spectrometry, Fluorescence
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Spectrophotometry, Ultraviolet
  • Tandem Mass Spectrometry / methods*

Substances

  • Anti-Arrhythmia Agents
  • Culture Media
  • Drugs, Chinese Herbal
  • Mexiletine
  • 6-hydroxymethylmexiletine
  • 4-hydroxymexiletine