基于UHPLC-Q-TOF-MS技术的洋川芎内酯A在大鼠体内的代谢产物分析  

Metabolite Identification of Senkyunolide A in Rats by Ultra-High Performance Liquid Chromatography Quadrupole-Time-of-Flight Mass Spectrometry

作　　者：张奥 段天华 徐荣荣 姜晓娅 张泽昭 张雯美 冯薇 王鑫国 ZHANG Ao;DUAN Tian-hua;XU Rong-rong;JIANG Xiao-ya;ZHANG Ze-zhao;ZHANG Wen-mei;FENG Wei;WANG Xin-guo(School of Pharmaceutical Sciences,Hebei TCM Formula Granule Technology Innovation Center,TCM Formula Granule research Center of Hebei Province University,Hebei University of Chinese Medicine,Shijiazhuang 050091,China)

机构地区：[1]河北中医学院药学院,河北省中药配方颗粒技术创新中心,河北省高校中药配方颗粒应用技术研发中心,河北石家庄050091

出　　处：《中国药学杂志》2023年第14期1287-1294,共8页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(82104358);河北省省级科技计划项目资助(21372503D,22E50139D);河北省自然科学基金面上项目资助(H2021423066)。

摘　　要：目的分析鉴定大鼠灌胃洋川芎内酯A后血浆、尿液、胆汁及粪便内存在的代谢产物并推测其在大鼠体内的代谢途径。方法SD(sprague dawley,SD)大鼠一次性灌胃给药后,收集不同时间(段)的血浆、尿液、胆汁及粪便,前处理后,采用超高效液相色谱-四极杆飞行时间质谱(ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry,UHPLC-Q-TOF-MS)技术,对代谢物进行结构表征。结果最终在大鼠血浆、尿液、胆汁和粪便中共检测到43个代谢产物,其中38个为首次在洋川芎内酯A代谢产物中分析确认,其体内代谢主要发生氧化、去甲基化、内水解和饱和双键加氢等Ⅰ相代谢,以及硫酸盐结合、谷氨酰胺结合、牛磺酸结合、半胱氨酸结合和葡萄糖醛酸化等Ⅱ相代谢。结论本研究初步揭示了洋川芎内酯A在大鼠血浆、尿液、胆汁和粪便中的代谢情况,为后期洋川芎内酯A活性代谢物筛选及作用机制研究提供参考。OBJECTIVE To analyze and identify the metabolites in plasma,urine,bile,and feces of rats after intragastric administration of senkyunolide A and to speculate on its metabolic pathway in rats.METHODS After the one-time intragastric administration of SD rats,plasma,urine,bile,and feces were collected at different times(segments),and the samples were pretreated.The structure of metabolites was characterized by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry.RESULTS Finally,a total of 43 metabolites were detected in rat plasma,urine,bile and feces,of which 38 were analyzed and confirmed for the first time in the metabolites of senkyunolide A.Their in vivo metabolism mainly includes phaseⅠmetabolism such as oxidation,demethylation,internal hydrolysis and saturated double bond hydrogenation,and phaseⅡmetabolism such as sulfate binding,glutamine binding,taurine binding,cysteine binding and glucuronidation.CONCLUSION This study preliminarily reveals the metabolism of senkyunolide A in rat plasma,urine,bile and feces,and provids a reference for the screening of active metabolites of senkyunolide A and its mechanism of action.

关 键 词：超高效液相色谱-四极杆飞行时间质谱 洋川芎内酯A 代谢产物 代谢途径 

分 类 号：R969[医药卫生—药理学]