HPLC-HRMS鉴定抗癌先导物T-OA在鼠尿中的代谢产物  

Identification of metabolites of antitumor lead compound T-OA in rat urine by HPLC-HRMS

作　　者：绪扩[1] 龚晏[1] 徐冰[1] 田雨霏 王明希 张华铮[2] 张宇忠[2] 雷海民[1] 

机构地区：[1]北京中医药大学中药学院,北京100102 [2]北京中医药大学基础医学院,北京100029

出　　处：《中国中药杂志》2014年第5期911-915,共5页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81173519);北京中医药大学创新团队项目(2011-CXTD-15)

摘　　要：目的:研究抗癌先导化合物T-OA(齐墩果酰基-3,5,6-三甲基吡嗪-2-甲酯)在大鼠尿液中的代谢产物,初步推断其在大鼠体内的代谢方式。方法:收集空白组、原料组(川芎嗪TMP与齐墩果酸OA摩尔等量)及T-OA组大鼠尿液;尿液冷冻干燥,固体经乙酸乙酯超声提取后,提取物用色谱乙腈复溶;HPLC-HRMS联用技术在ESI+和ESI-模式下寻找可能的质谱峰,通过对比3组谱图的异同得出代谢产物的相关信息。结果:原料组鉴定出1个OA的代谢产物和2个TMP的代谢产物;T-OA组未检测到原料的代谢产物,而得到1个Ⅱ相代谢产物。结论:在大鼠尿液中首次鉴定出1个T-OA的Ⅱ相代谢产物,1个OA的Ⅱ相代谢产物,初步推断T-OA在体内不以原料的形式发挥药效;所建立的HPLC-HRMS方法可用于相关衍生结构的代谢产物鉴定;该文也可为以齐墩果酸为母体的前药设计提供一定的借鉴。Objective： To study the major metabolites of antitumor lead compound T-OA （oleanolic acyl-3, 5, 6-trimethyl pyrazine-2-methyl ester） in rat urine, in order to preliminarily infer its metabolic mode in rats. Method： Rat urines of the blank group, the raw material group （ligustrazinc TMP and oleanolie acid OA Moore equivalent） and the T-OA group were collected and freeze-dried; Solids were extracted by ethyl acetate; And then the extracts were re-dissolved with acetonitrile. HPLC-HRMS coupling technique was adopted to find the potential mass spectrum peak under ESI ~ ~＇N ESI - modes. Metabolite-related information was obtained by comparing the three groups of spectra. Result： One metabolite of OA and two metabolites of TMP were identified in the raw material group ; none metabolite of T-OA but one phase ]] metabolite was detected in the T-OA group. Conclusion ： It is the first time to identi- fy one phase ]I metabolite of T-OA and one phase II metabolite of OA were identified in rat urine. On that basis, the researchers pre- liminarily inferred that T-OA does not show the efficacy in the form of raw material. The HPLC-HRMS method established could be used to identify metabolites of related derivative structures. This paper could also provide certain reference for designing pro-drugs based on oleanolie acid.

关 键 词：抗癌先导物T-OA 大鼠尿液 代谢产物 HPLC—HRMS 

分 类 号：R284[医药卫生—中药学]