Metabolite profiling and identification of triptolide in rats
Metabolite profiling and identification of triptolide in rats
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雷公藤内酯醇在大鼠体内的代谢谱和鉴定
DOI：
10.1016/j.jchromb.2013.08.015
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发表时间：
2013-11-15
影响因子：
3
通讯作者：
Zhong, Dafang
中科院分区：
文献类型：
--
作者：
Liu, Jia;Li, Liang;Zhong, Dafang
本研究的目的是研究[H-3]雷公藤甲素在大鼠体内的代谢谱。用于鉴定主要代谢物的分离和表征技术是高效液相色谱-在线无线电探测器，超高效液相色谱-四极杆飞行时间质谱和核磁共振。总共检测到33种主要代谢物。在大鼠血浆中发现的主要成分包括母体药物及其单羟基和双羟基代谢物。用母药与大鼠肝微粒体孵育或用黑坎宁哈默菌转化获得单羟基代谢物的标准品。代谢产物结构鉴定为17-羟基雷公藤甲素、16-羟基雷公藤甲素、雷公藤甲素和15-羟基雷公藤甲素。在雄性大鼠尿液中发现的主要代谢物包括单羟基代谢物、二羟基代谢物和三羟基代谢物。雌性大鼠尿液中的主要代谢物是单羟基代谢物和双羟基代谢物，以及单羟基代谢物的硫酸盐。在雄性大鼠的胆汁和粪便中检测到谷胱甘肽加合物、多种羟基代谢物和一些未识别的代谢物。在雌性大鼠的胆汁和粪便中检测到单羟基代谢物的硫酸盐。(C) 2013 Elsevier B.V.版权所有
The purpose of the current study was to investigate the metabolite profile of [H-3]triptolide in rats. The separation and characterisation techniques used to identify the major metabolites were high-performance liquid chromatography-online radiodetector, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry, and nuclear magnetic resonance. In all, 33 major metabolites were detected. The major components found in the rat plasma included the parent drug and its monohydroxy- and dihydroxy-metabolites. Reference standards for the monohydroxy-metabolites were obtained either by the incubation of the parent drug with rat liver microsomes or by microbial transformation with Cunninghamella blakesleana. The metabolites' structures were identified as 17-hydroxytriptolide, 16-hydroxytriptolide, tripdiolide, and 15-hydroxytriptolide. The major metabolites found in male rat urine included the monohydroxy-, dihydroxy-, and trihydroxy-metabolites. The major metabolites in female rat urine were the monohydroxy- and dihydroxy-metabolites, as well as sulphates of the monohydroxy-metabolites. A glutathione adduct, multiple hydroxy-metabolites, and a number of unidentified metabolites were detected in the bile and faeces of male rats. Sulphates of monohydroxy-metabolites were detected in the bile and faeces of female rats. (C) 2013 Elsevier B.V. All rights reserved.