Assay of tocainide enantiomers in plasma by solid-phase extraction and indirect chiral high-performance liquid chromatography after derivatization with (-)-menthyl chloroformate.

E B Christensen, S H Hansen, S N Rasmussen

Index: J. Chromatogr. B, Biomed. Appl. 670(2) , 243-9, (1995)

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Abstract

A fast high-performance liquid chromatographic (HPLC) assay was developed for determination of tocainide enantiomers in plasma. Subsequent to solid-phase extraction of tocainide from plasma, homochiral derivatization with (-)-menthyl chloroformate enabled separation of the enantiomers 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 micrograms/ml tocainide enantiomer and the limit of quantitation was 1.0 microgram/ml. The method was applied to a study of the distribution and elimination pharmacokinetics of tocainide enantiomers in the rabbit. No difference in distribution or elimination between the enantiomers was found nor did the enantiomers affect the disposition of one another when administered together as the racemate.