High-performance liquid chromatographic determination of mexiletine enantiomers in plasma using direct and indirect enantioselective separations

Journal of Chromatography. B, Biomedical Applications
V L LanchoteC Bertucci

Abstract

Two methods were developed for the determination of mexiletine enantiomers in plasma samples suitable for studies on the stereoselective disposition of this drug. Both methods used fluorescence detection to improve sensitivity and selectivity. The direct enantioselective separation was based on the chiral resolution of mexiletine-2-naphthamide derivatives on a Chiralcel OJ column. The calibration curves were linear over the concentration range 50-500 ng/ml for each enantiomer; therefore the method can be used only for therapeutic monitoring, drug interaction and multiple dose pharmacokinetic studies. The indirect method was based on the formation of diastereomers using o-phthaldialdehyde and N-acetyl-L-cysteine reagents. The diastereomers were resolved on a reversed-phase RP-18 column. The method proved to be suitable for single or multiple dose pharmacokinetic studies based on the low quantification limit (1 ng/ml) and the broader linear range (1-1000 ng/ml) obtained.

Citations

Jun 22, 1999·Biomedical Chromatography : BMC·J Bojarski, H Y Aboul-Enein
Sep 2, 1998·European Journal of Drug Metabolism and Pharmacokinetics·V L LanchoteS R Santos
Oct 22, 2008·Journal of Pharmaceutical and Biomedical Analysis·Paraskevas D TzanavarasPantelis Rigas
Nov 23, 2006·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Shuijun LiJianying Ren
May 11, 2012·The Journal of Pharmacy and Pharmacology·Lushan YuSu Zeng
Sep 23, 2020·Biomedical Chromatography : BMC·Sonika SethiRavi Bhushan

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