Abstract: A method for the assay of R-(-)- and S-(+)-mexiletine in rat liver microsomal incubates was developed. The method involved extraction of mexiletine from the microsomal incubates, and formation of mexiletine diastereomeric derivatives with a chiral reagent S-(-)-N-trifluoroacetyl prolyl chloride. Separation and quantitation of the diastereomeric mexiletine derivatives were carried out by a capillary gas chromatographic system with flame ionization detection. The assay was linear from 5 to 500 μg/ml for each enantiomer. The average recoveries of analytical method were 93.31%±5.59% and 93.10%±5.11% for R-(-)- and S-(+)-mexiletine, respectively. The limits of detection and quantitation for the method were 1.0 μg/ml and 5.0 μg/ml for the R-(-)- and S-(+)-mexiletine isomers, respectively. The reproducibility in the assay was better than 16.5% (RSD). The method has been applied to the metabolism study of R-(-)- and S-(+)-mexiletine in rat liver microsomal incubates.

Key words: Mexiletine, Capillary gas chromatography, Enantiomer separation