Fan G R, Hong Z Y, Lin M, Yin X P, Wu Y T
Shanghai Key Laboratory for Pharmaceutical Metabolites Research, School of Pharmacy, Second Military Medical University, No. 101 Guohe Road, Shanghai, 200433, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Oct 5;809(2):265-71. doi: 10.1016/j.jchromb.2004.06.030.
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-gamma-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 degrees 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.
本研究的目的是测定消旋山莨菪碱经口和静脉给药后家兔血浆中山莨菪碱对映体的药代动力学。首次建立并验证了一种用于同时分离血浆中两对映体的毛细管电泳方法。使用含25 mM羧甲基化γ-环糊精的75 mM磷酸盐缓冲液，pH 2.5，在45 cm未涂层熔融石英毛细管上，于20 kV电压和25℃下实现了良好的分离度。使用CE测定法（山莨菪碱对映体分离的唯一方法）对各山莨菪碱对映体的药代动力学进行了表征。结果的药代动力学分析表明，山莨菪碱对映体在不同家兔中表现出非立体选择性分布或立体选择性分布。对于具有非立体选择性分布的家兔，(6S, 2'S)-和(6R, 2'R)-，或(6S, 2'R)-和(VR, 2'S)-山莨菪碱之间观察到相似的药代动力学特征。对于具有立体选择性分布的家兔，(6S, 2'S)-和(6R, 2'S)-山莨菪碱低于既定的检测限，而其余两种对映体也具有相似的药代动力学特征。仍有必要进行进一步研究以找出(6S, 2'S)-和(6R, 2'S)-山莨菪碱立体选择性分布的潜在机制。
