Pharmacokinetic study and metabolite identification of the bidesmosidic triterpenoid saponin BTS-1 in rat plasma

Assays based on high-performance liquid chromatography(HPLC)and liquid chromatography tandem mass spectrometry(LC–MSn)have been developed and validated for the determination and metabolite identification of the bidesmosidic triterpenoid saponin,BTS-1(3-O-β-D-galactopyranosyl-(1-2)-[β-D-xylopyranosyl-(1-3)]-β-D-glucuronopyranosyl gypsogenin 28-O-α-L-arabinopyranosyl-(1-3)-βD-xylopyranosyl-(1-4)-α-L-rhamnopyranosyl-(1-2)-β-D-fucopyranoside),in rat plasma.The assay was successfully applied to a pharmacokinetic study in rats given a single oral dose of BTS-1(400 mg/kg).The results indicated that the compound was rapidly absorbed(Tmax=1.2870.29 h,Cmax=37.475.6 mg/mL)and slowly eliminated(t1/2=13.276.6 h).In addition,secondary glycosides and aglycones of BTS-1 were detected and identified.Since these metabolites are known to be activeα-glucosidase inhibitors,they probably play an important role in mediating the pharmacological effects of the saponin.

6,7-二甲氧基香豆素在大鼠体内主要代谢产物的研究

目的:研究大鼠单剂量ig5mg/kg6,7-二甲氧基香豆素后各生物样品中主要代谢产物。方法:采用高效液相色谱法对代谢物进行分析和分离,并利用电喷雾离子阱质谱注射泵直接进样技术及液相色谱-质谱联用技术(LC/MSn)对大鼠尿液、胆汁中6,7-二甲氧基香豆素主要代谢产物进行结构鉴定。结果:大鼠给药后0～10h内,仅在血样中检测到母体药物6,7-二甲氧基香豆素,而在尿样、粪样及胆汁中均未检出。比较服药前后的生物样品色谱行为可见,大鼠口服6,7-二甲氧基香豆素后,在胆汁中存在两个主要代谢产物(M1和M2),在血样和尿样中则以M1为主,而在粪样中未检出。由其色谱峰面积估计,代谢物M1和M2的含量占生物样品中代谢物总量的80%以上。结论:根据代谢物的色谱行为及质谱断裂规律,推定6,7-二甲氧基香豆素在大鼠体内的两个主要代谢产物(M1和M2)为6,7-二甲氧基香豆素经水解脱甲基生成的羟基化合物,均以硫酸酯结合物形式存在,且互为同分异构体。

大鼠口服棉花皮素-8-O-β-D-葡萄糖醛酸苷后尿液中代谢产物研究

目的:研究大鼠口服棉花皮素-8-O-β-D-葡萄糖醛酸苷后尿液中的代谢产物。方法:健康大鼠口服250mg·kg-1棉花皮素-8-O-β-D-葡萄糖醛酸苷后,收集0～48h的尿样,经HPD-600大孔吸附树脂分离纯化后采用HPLC-DAD-MSn方法对尿样中的原形药物及其代谢产物进行分析及结构推测。结果:在大鼠尿液中检测到棉花皮素-8-O-β-D-葡萄糖醛酸苷的6个主要代谢产物,根据负离子模式下电喷雾质谱的裂解规律、紫外光谱特征以及与标准品对照的方法,鉴定了其中1个代谢产物的结构,推测了其他5个代谢产物的结构,其代谢过程主要是葡萄糖醛酸化、脱葡萄糖醛酸以及甲基化等。结论:本文建立的方法快速、灵敏,可用于棉花皮素-8-O-β-D-葡萄糖醛酸苷及其体内外代谢产物的研究。