Separation of chlorobenzyltetrahydroberberine enantiomers by capillary electrophoresis and their chiral pharmacokinetic studies in rabbits

Objective: To establish a capillary electrophoresi method for the separation and determination of chlorobenzyltetrahydroderberine (CBTHB ) enantiomers and investigate their chiral pharmacokinetics in rabbits. Methods: Race mic CBTHB was separated optimally and measured successfully with capillary electrophoresis, based on comparison of chiral recognition capabilities of carboxymethylated cyclodextrins and selection of other electrophoretic conditions. The plasma con centration data were handled with the theory of statistical moment and the pharmacokinetic parameters were obtained. Results: CBTFHB enantiomers in rabbit plasma samples were Separated under optimal chiral conditions without interruption of endogenous components. After a single oral dose of’ 150 mg/kg racemic CBTHB in 6 rabbits, plasma level of R-CBTHB en antiomer was always higher than that of S-CBTHB enantiomer, the ratio of R- to S-CBTHB was 1. 43 ± 0. 21 (range 1. 23 - 1. 91 ), resulting in significant differences between the plasma concentrations of R-CBTHB and those of S-CBTHB. Furthermore, it was found that the area under concentration-time curve AUC0-τ and AUC0-∞ of R-CBTHB were significantly greater than that of S-CHTHB. Conclusion: The new chiral capillary electrophoresis method proves to be suitable for studies on CBTHB enantiomers pharmacokinetics.