Determination of the enantiomers of a new 1,4-dihydropyridine calcium antagonist in dog plasma by achiral/chiral coupled high-performance liquid chromatography with electrochemical detection.

An achiral/chiral coupled high-performance liquid chromatographic method with electrochemical detection was developed for the determination of the enantiomers of a new dihydropyridine calcium blocker, methyl (+-)-4,7-dihydro-3-isobutyl-6-methyl-4-(3-nitrophenyl)- thieno[2,3-b]pyridine-5-carboxylate (1), in dog plasma. The assay showed linearity over the range 1-200 ng/mL for the two enantiomers. The limit of determination was 1 ng/mL for each analyte. The assay precision was < 9%, with relative errors of -5.7 to +6.9% at 3 and 30 ng/mL levels of both the enantiomers. The method was applied to a pharmacokinetic study of the enantiomers of 1 in beagle dogs after oral administration of racemic 1.