采用UHPLC-MS和质量亏损过滤技术分析二苯乙烯苷在大鼠体内的代谢产物和代谢途径  

Analysis of Metabolites and Metabolism Pathway of Tetrahydroxystilbene Glucoside in Rats with UHPLC-MS and Mass Defect Filter Method

作　　者：梁幼玲 史旭华 白俊其 黄志海[1] 徐文[1] 黄娟[1] 丘小惠[1,2] LIANG Youling;SHI Xuhua;BAI Junqi;HUANG Zhihai;XU Wen;HUANG Juan;QIU Xiaohui(Guangdong Province Hospital of TCMSecond College of Clinical Medicine,Guangzhou University of TCM,Guangzhou 510120,China;Guangzhou Key Laboratory of Chirality Research on Active Components of TCM,Guangzhou 510006,China)

机构地区：[1]广东省中医院/广州中医药大学第二临床医学院,广州510120 [2]广州市中药活性成分手性研究重点实验室,广州510006

出　　处：《中国药房》2021年第6期675-681,共7页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81373967);广州市科技计划项目(No.201806010048,No.202002010004);广东省中医院中医药科学技术研究专项课题(No.YN2019QJ14)。

摘　　要：目的:分析二苯乙烯苷在大鼠体内的代谢产物并推测代谢途径。方法:将雄性SD大鼠随机分为血浆组(n=3)、尿液组(n=3)、胆汁组(n=3)和组织组(n=9),各组大鼠均单次灌胃二苯乙烯苷200 mg/kg,分别收集给药后10、30 min和1、1.5、2、4 h的血浆,给药后0~6 h的尿液,给药后0~4 h的胆汁以及给药后30 min和1、2 h(每个时间点3只)的心、肝、脾、肺、肾、胃组织样品,经甲醇沉淀蛋白后,采用超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用技术和质量亏损过滤技术联合分析、鉴定各样本中的代谢产物,推测代谢途径。结果:从血浆、尿液、胆汁、心、肝、脾、肺、肾、胃样品中分别检出6、7、11、1、5、1、3、4、4个代谢产物,包括Ⅰ相代谢(如水解、加氢、羟化)产物2个、Ⅱ相代谢(如葡萄糖醛酸结合和硫酸化)产物18个,其中葡萄糖醛酸结合产物有12个。结论:二苯乙烯苷在胆汁中的代谢产物种类居多,以Ⅱ相代谢产物二苯乙烯苷的葡萄糖醛酸结合产物为主;代谢途径主要涉及葡萄糖水解、加氢、羟化、葡萄糖醛酸结合、硫酸化反应等。OBJECTIVE:To analyze the metabolites of tetrahydroxystilbene glucoside(THSG)and speculate its metabolism pathway in rats.METHODS:Male SD rats were randomly divided into plasma group(n=3),urine group(n=3),bile group(n=3),and tissue group(n=9).Each group was given single dose of THSG 200 mg/kg intragastrically.Plasma samples 10,30 min and 1,1.5,2,4 h after medication,the unrine 0-6 h after medication,the bile 0-4 h after medication,the tissue of heart,liver,spleen,lung,kidney and stomach 30 min and 1,2 h after medication(3 at each time point)were collected respectively.After precipitated with methanol,the metabolites of samples were analyzed and identified by UHPLC-Q-Exactive Orbitrap MS and mass loss filtration(MDF).Its metabolism pathway was speculated.RESULTS:In the blood,urine,bile,heart,liver,spleen,lung,kidney,stomach samples,6,7,11,1,5,1,3,4,4 metabolites were detected,including two phaseⅠ(hydrolysis,hydrogenation and hydroxylation)metabolites,18 phaseⅡ(glucuronic acid binding and sulfation)metabolites.There were 12 glucuronic acid binding products.CONCLUSIONS:Most of the metabolites of THSG are found in bile,mainly glucuronic acid binding products of phaseⅡmetabolite THSG;main metabolic pathways involve glucose hydrolysis,hydrogenation,hydroxylation,glucuronic acid binding and sulfation.

关 键 词：二苯乙烯苷 超高效液相色谱-四极杆-静电场轨道阱高分辨质谱联用技术 质量亏损过滤技术 代谢产物 大鼠 

分 类 号：R969.1[医药卫生—药理学]