17―氢―9―去氢穿心莲内酯体外代谢速率及代谢产物的研究.docVIP

17―氢―9―去氢穿心莲内酯体外代谢速率及代谢产物的研究 　　[摘要] 应用体外大鼠肝微粒体孵育体系，研究喜炎平注射液中主要有效成分17-氢-9-去氢穿心莲内酯（DHA）的体外代谢速率及代谢产物。将17-氢-9-去氢穿心莲内酯与加入NADPH的大鼠肝微粒体共同孵育，采用超高效液相色谱-三重四极杆串联质谱法（UHPLC-MS/MS）测定其剩余浓度，考察17-氢-9-去氢穿心莲内酯的肝微粒体代谢速率，并采用超高效液相色谱串联飞行时间质谱（UPLC-TOF-MSlt;supgt;Elt;/supgt;）对孵育体系中17-氢-9-去氢穿心莲内酯的代谢产物进行鉴定。研究结果显示在加入辅酶的大鼠肝微粒体中，17-氢-9-去氢穿心莲内酯代谢速率较快，其半衰期（tlt;subgt;1/2lt;/subgt;）和肝微粒体中清除率（CL）分别为（19.7±0.5） min和（35.1±0.8） mL?minlt;supgt;-1lt;/supgt;?glt;supgt;-1lt;/supgt;。高分辨质谱数据结合文献信息共鉴定孵育体系中17-氢-9-去氢穿心莲内酯的9个代谢产物，主要为羟基化产物和脱氢产物。鉴定结果为筛选出活性更好的穿心莲二萜内酯类衍生物提供了一定的依据。 　　[关键词] 17-氢-9-去氢穿心莲内酯;肝微粒体;UHPLC-MS/MS;代谢速率;UPLC-TOF-MSlt;supgt;Elt;/supgt;;代谢产物 　　[收稿日期] 2014-08-07 　　[基金项目] 江西省科技计划项目（2012BBG70020） 　　[通信作者] 罗跃华，Tel：（0791E-mail：emailluo@ 　　[作者简介] 邵军，硕士研究生，E-mail：452224929@ 　　Study on in vitro metabolic rate and metabolites of 9-dehydro- 　　17-dehydro-andrographolide 　　SHAO Jun， CHEN Wei-kang， ZHENG Dong-kun， MA Shuang-cheng， LUO Yue-hua 　　（1. Jiangxi Provincial Research Institute for Drug Control， Nanchang 330029， China; 　　2. School of Pharmacy， Nanchang University， Nanchang 330046， China; 　　3. National Institutes for Food and Drug Control， Beijing 100050， China） 　　[Abstract] To investigate the metabolic rate and metabolites of 9-dehydro-17-dehydro-andrographolide， which is the main active ingredient in Xiyanping injection， by using the in vitro rat liver microsome incubation system. 9-dehydro-17-dehydro-andrographolide was incubated together with liver microsome mixed with NADPH. Its metabolic rate was studied by determining its residual concentrations with the UHPLC-MS/MS method; Its metabolites were identified by the UPLC-TOF-MSlt;supgt;Elt;/supgt; method. The results showed that 9-dehydro-17-dehydro-andrographolide was metabolized faster than rat liver microsomes mixed with coenzymes， with tlt;subgt;1/2lt;/subgt;and CL of （19.7±0.5） min and （35.1±0.8） mL?minlt;supgt;-1lt;/supgt;?glt;supgt;-1lt;/supgt;（protein）， respectively. Based on the high resolution mass spectrum data and i