Gas--liquid chromatographic resolution and assay of tocainide enantiomers using a chiral capillary column and study of their selective disposition in man.

Tocainide is a new antiarrhythmic agent that is used clinically as the racemic mixture. In order to study the disposition of the individual enantiomers in man, a gas--liquid chromatographic assay was developed based on the resolution of the R-(-)- and S-(+)-enantiomers as their heptafluorobutyryl derivatives on a capillary column coated with a chiral stationary phase. Two healthy male volunteers ingested an oral solution dose of racemic tocainide hydrochloride at a dose of 3 mg/kg and plasma and urine were collected at intervals for up to 54 h. Analysis of the plasma samples revealed a stereoselective disappearance of the R-(-)-enantiomer, such that the apparent half-life for the S-(+)- and R-(-)-enantiomers were 25.6 and 20.5 h, respectively in one subject and 11.1 and 9.0 h in the second subject. Similar relationships were observed in urine, where the ratio of the S-(+)- to R-(-)-enantiomers varied from 0.98 in 1 h to 3.03 in the 54-h samples in one subject over the same time period.