甜茶素在大鼠体内的代谢产物鉴定与药动学研究  

Identification of metabolites and pharmacokinetic study of rubusoside in rats

作　　者：姜蔓菁 蒙金英 颜夏晴 覃淑婷 李耀华 樊兰兰 JIANG Man-jing;MENG Jin-ying;YAN Xia-qing;QIN Shu-ting;LI Yao-hua;FAN Lan-lan(School of Pharmacy,Guangxi University of Chinese Medicine,Nanning 530200,China)

机构地区：[1]广西中医药大学药学院,广西南宁530200

出　　处：《中草药》2021年第13期3914-3922,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(31660095);国家自然科学基金资助项目(81903918);广西自然科学基金资助项目(2019JJA140644);广西中医药大学一流学科项目(2019XK117);广西中医药大学研究生创新项目(YCSZ2020011,YCSZ20190028)。

摘　　要：目的对甜茶素在大鼠体内的代谢产物进行定性分析,并考察甜茶素在大鼠体内的药动学特征。方法SD大鼠ig甜茶素(125 mg/kg),收集不同时间段的尿液、粪便、胆汁和血浆。采用超高效液相色谱-四级杆飞行时间质谱联用技术(UPLC-Q-TOF-MS/MS)分析其在大鼠体内的代谢产物;基于超高效液相色谱串联质谱(UPLC-MS/MS)建立一种测定大鼠血浆中甜茶素含量的方法,初步研究甜茶素的药动学特征。结果大鼠ig甜茶素后,在尿液、粪便、胆汁和血浆中共检测并初步鉴定了1种原型成分和58种代谢物,主要代谢途径有脱氢化、羟基化、去葡萄糖基化、葡萄糖醛酸化、硫酸酯化等。甜茶素在大鼠体内的吸收较快,在0.12 h血药浓度达到最大值,半衰期为4.20 h,较大的表观分布容积提示甜茶素可能存在一定的组织分布。结论甜茶素在大鼠体内吸收迅速,并经历广泛的代谢反应,为进一步阐明甜茶素药效物质基础提供依据。Objective To identify the metabolites and study the pharmacokinetic characteristics of rubusoside in rats.Methods SD rats were ig rubusoside(125 mg/kg),metabolites in their urine,feces,bile and plasma collected at different time periods were identified by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-QTOF-MS/MS).A UPLC-MS/MS method was developed and validated for determination of rubusoside in rat plasma.The pharmacokinetic characteristics of rubusoside in rats were investigated.Results One prototype component and 58 metabolites were detected.The main metabolic pathways of rubusoside were dehydrogenation,hydroxylation,deglucosylation,glucuronic acid conjugation,sulfation,etc.Rubusoside was absorbed rapidly into the blood after intragastric administration.Maximum concentration(tmax)and the half-life(t1/2)of rubusoside were 0.12 h and 4.20 h,respectively.Meanwhile,the large apparent volume of distribution indicated possible tissue distribution of rubusoside.Conclusion Rubusoside was absorbed fast and experienced extensive metabolism in vivo in rats,which provide a reference for further investigation on therapeutic material basis of rubusoside.

关 键 词：甜茶素 代谢产物 药动学 UPLC-Q-TOF-MS/MS UPLC-MS/MS 

分 类 号：R285.61[医药卫生—中药学]