ASSAY OF TOCAINIDE ENANTIOMERS IN PLASMA BY SOLID-PHASE EXTRACTION AND INDIRECT CHIRAL HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY AFTER DERIVATIZATION WITH (-)-MENTHYL CHLOROFORMATE

A fast high-performance liquid chromatographic (HPLC) assay was develo ped for determination of tocainide enantiomers in plasma. Subsequent t o solid-phase extraction of tocainide from plasma, homochiral derivati zation with (-)-menthyl chloroformate enabled separation of the enanti omers by a conventional reversed-phase HPLC system. The detection was performed by UV absorption at 262 nm. An enantiomeric resolution of 1. 0 was obtained. Linearity of the method was investigated and found to be good in the range from 1.0 to 20.0 mu g/ml tocainide enantiomer and the limit of quantitation was 1.0 mu g/ml. The method was applied to a study of the distribution and elimination pharmacokinetics of tocain ide enantiomers in the rabbit. No difference in distribution or elimin ation between the enantiomers was found nor did the enantiomers affect the disposition of one another when administered together as the race mate.