HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF MEXILETINE ENANTIOMERS IN PLASMA USING DIRECT AND INDIRECT ENANTIOSELECTIVE SEPARATIONS

Two methods were developed for the determination of mexiletine enantio mers in plasma samples suitable for studies on the stereoselective dis position of this drug. Both methods used fluorescence detection to imp rove sensitivity and selectivity. The direct enantioselective separati on was based on the chiral resolution of mexiletine-2-naphthamide deri vatives on a Chiralcel OJ column. The calibration curves were linear o ver the concentration range 50-500 ng/ml for each enantiomer; therefor e the method can be used only for therapeutic monitoring, drug interac tion and multiple dose pharmacokinetic studies. The indirect method wa s based on the formation of diastereomers using o-phthaldialdehyde and N-acetyl-L-cysteine reagents. The diastereomers were resolved on a re versed-phase RP-18 column. The method proved to be suitable for single or multiple dose pharmacokinetic studies based on the low quantificat ion limit (1 ng/ml) and the broader linear range (1-1000 ng/ml) obtain ed.