20(S)-原人参二醇奥克梯隆型差向异构体大鼠排泄研究

Study on excretion of 20( S)-protopanaxadiolocotillol type epimers in rats

20(S)-原人参二醇奥克梯隆型差向异构体为20(S)-原人参二醇的主要代谢产物,前期研究发现,该差向异构体在药效学和药动学方面均有一定的立体选择性。该文建立了HPLC-MS/MS测定大鼠尿液、粪便和胆汁中的24R-差向异构体和24S-差向异构体,考察口服灌胃给予大鼠24R-差向异构体或24S-差向异构体后,在尿液、粪便和胆汁中的排泄情况。结果显示,24R-差向异构体和24S-差向异构体在口服给药后48 h内粪便排泄累积量分别为给药剂量的17.69%,17.09%,基本不经尿排泄。口服给药后48 h内,24R-差向异构体和24S-差向异构体胆汁排泄累积量分别为给药剂量的8.01%,1.47%,前者是后者的5.4倍,具有明显的立体选择性。

Gindenosides are the active ingredients of Panax ginseng. 20（S）-protopanaxadiolocotillol type epimers are the main metabolites of 20（S）-protopanaxadiol. The previous studies showed that there are stereoselectivity difference in pharmacodynamics and pharmacokinetics between 24R-epimer and 24S-epimer. The purpose of this study was to explore the excretion of the epimers in bile, feces and urine of rat. Liquid chromatography tandem mass spectrometry method has been performed for determination of 24R-epimer and 24S-epimer in bile, feces and urine. 24R-epimer or 24S-epimer was intragastric administered to rats at a single dose of 10 mg·kg-1. Results showed that after administration the recovery of 24R-epimer and 24S-epimer in feces was 17.69% and 17.09%, respectively, while both of the two epimers were hardly detected in urine. The 48 h cumulative biliary excretion rate of 24R-epimer was 8.01% after administration, while only 1.47% for 24S-epimer. It indicated that there are stereoselectivity in biliary excretion of the epimers with intragastric administration.