Study of stereoselective pharmacokinetics of anisodamine enantiomers in rabbits by capillary electrophoresis

摘要

The purpose of this study was to determine the pharmacokinetics of anisodamine enantiomers in plasma after oral and intravenous administration of racemic anisodamine in rabbits. A capillary electrophoresis method for the simultaneous separation of two pairs of enantiomers in plasma has been firstly developed and validated. Using a 75 mM phosphate buffer containing 25 mM carboxymethylated-γ-cyclodextrin at pH 2.5, good resolution was achieved on a 45-cm uncoated fused-silica capillary at the voltage of 20 kV and 25 °C. The pharmacokinetics of individual anisodamine enantiomers were characterized using the CE assay, the sole method of enantiomeric separation for anisodamine. Pharmacokinetic analysis of results indicated that anisodamine enantiomers showed non-stereoselective disposition or stereoselective disposition in different rabbits. For the rabbits with non-stereoselective disposition, similar pharmacokinetic characteristics were observed between (6S, 2′S)- and (6R, 2′R)-, or (6S, 2′R)- and (6R, 2′S)-anisodamine. For the rabbits with stereoselective disposition, (6S, 2′S)- and (6R, 2′S)-anisodamine were below the established LOD, while the two remaining enantiomers also had similar pharmacokinetic profiles. Further investigations remain necessary to find out the underlying mechanism about the stereoselective disposition of (6S, 2′S)- and (6R, 2′S)-anisodamine.