桂枝茯苓胶囊在原发性痛经模型大鼠血浆、胆汁、尿液和粪便中的代谢产物研究  

Analysis of metabolites in primary dysmenorrhea rats plasma,bile,urine and feces after administration of Guizhi Fuling capsules

作　　者：赵秋龙 卞晓坤 钱大玮[1] 宿树兰[2] 郭盛[2] 王团结[3] 段金廒[2] ZHAO Qiu-long;BIAN Xiao-kun;QIAN Da-wei;SU Shu-lan;GUO Sheng;WANG Tuan-jie;DUAN Jin-ao(Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/Jiangsu Key Laboratory for High Technology Research of TCM Formulae,Nanjing University of Chinese Medicine,Nanjing 210023,China;National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Nanjing University of Chinese Medicine,Nanjing 210023,China;Kanion Pharmaceutical Co.,Ltd.,Lianyungang 222001,China)

机构地区：[1]南京中医药大学江苏省中药资源产业化过程协同创新中心/江苏省方剂高技术研究重点实验室,南京210023 [2]南京中医药大学中药资源产业化与方剂创新药物国家地方联合工程研究中心,南京210023 [3]江苏康缘药业股份有限公司,连云港222001

出　　处：《药物分析杂志》2021年第1期51-63,共13页Chinese Journal of Pharmaceutical Analysis

基　　金：桂枝茯苓胶囊标准化建设(ZYBZH-C-JS-28)。

摘　　要：目的:研究桂枝茯苓胶囊在原发性痛经模型大鼠体内的代谢产物。方法:基于超高效液相色谱-线性离子阱-静电轨道阱串联质谱联用(UHPLC-LTQ-Orbitrap-MS)方法,采用Waters ACQUITY UPLC BEH C_(18)色谱柱(100 mm×2.1 mm,1.7μm),以乙腈-0.1%甲酸水为流动相,梯度洗脱,流速0.4 mL·min^(-1),质谱采用电喷雾(ESI)离子源,以正负离子模式采集多级质谱碎片信息,对大鼠灌服桂枝茯苓胶囊混悬液后的血浆、胆汁、尿液和粪便进行分析,利用质量亏损过滤(MDF)技术进行代谢产物鉴定分析。结果:共鉴定出8个原形及50个代谢产物,在体内主要发生Ⅰ相代谢反应(脱羧、水解、脱羟基和脱水等)及Ⅱ相代谢反应(甲基化、乙酰化、硫酸化及葡萄糖醛酸化等)。结论:采用LC-MS方法鉴定了原发性痛经模型大鼠体内桂枝茯苓胶囊代谢产物,为该复方制剂的药物代谢动力学研究提供依据。Objective:To determine the metabolites in primary dysmenorrhea rats after administration of Guizhi Fuling capsules.Methods:The ultra-high performance liquid chromatography-LTQ Orbitrap mass spectrometric(UHPLC-LTQ-Orbitrap-MS)and mass defect filter techniques with electrospray ion(ESI)source were applied to collect multi-level mass spectrometry fragment information in both positive and negative ion modes.The separation was performed on a Waters ACQUITY UPLC BEH C18 column(100 mm×2.1 mm,1.7μm)with mobile phase of acetonitrile-water(containing 0.1%formic acid)by gradient elution at a flow rate of 0.4 mL·min^(-1).After the administration of Guizhi Fuling capsules,the plasma,bile,urine and feces in rats were analyzed,and the metabolites were identified by mass loss filtration(MDF).Results:8 prototypes and 50 metabolites were determined.The in vivo main metabolic reactions were phaseⅠreaction(decarboxylation,hydrolysis,dehydroxylation and dehydration)and phaseⅡreaction(methylation,acetylation,sulfonation and glucuronidation).Conclusion:LC-MS isused to identify metabolites of Guizhi Fuling capsules in rats with primary dysmenorrhea,and this study provids a basis for pharmacokinetic studies of the compound preparation of traditional Chinese medicine.

关 键 词：桂枝茯苓胶囊 桂枝 茯苓 牡丹皮 桃仁 白芍 原发性痛经 代谢产物 超高效液相色谱-线性离子阱-静电轨道阱串联质谱 

分 类 号：R917[医药卫生—药物分析学]