雷公藤甲素体内代谢产物研究

Identification of Metabolites from Triptolide in Vivo

目的:研究配伍甘草后雷公藤甲素在大鼠体内的代谢产物,为阐明甘草对雷公藤的减毒增效机制以及指导雷公藤甲素代谢产物的分离鉴定奠定基础。方法:采用高效液相色谱二极管阵列结合电喷雾离子肼多级质谱(HPLC-DAD-ESI/Trap/MSn)法研究配伍甘草后雷公藤甲素在大鼠尿液中的代谢产物。结果:在大鼠尿液中发现雷公藤甲素代谢产物4个,分子量分别为376(M1),376(M2),374(M3)和390(M4)。根据DAD紫外光谱图、电喷雾离子肼多级质谱以及药物体内代谢特点初步鉴定为:2(或5)-羟基雷公藤甲素(M1,M2),2-羰基雷公藤甲素(M3),2-羰基-5-羟基雷公藤甲素(M4)。结论:氧化代谢产物为雷公藤甲素的主要代谢产物,氧化代谢可能为雷公藤甲素的解毒途径。

Objective：To identify the metabolites of triptolide combined withG yl cyrrhiza uralensis in vivo and disclose the attenuation mechanism of Glycyrrhiza uralensis on Tripterygium wilfordii.Methods：The SD rats were injected with triptolide after orally taken with extracts of Glycyrrhiza uralensis.The metabolites of triptolide in rat urine were identified by HPLC-DAD-ESI/Trap/MSn method. Results：Four metabolites （ molecular weight of 376, 376, 374, 390 ） of triptolide in rat urine were found and initially identified as 2 （5）-OH-triptolide（M1,M2）, 2-oxo-triptolide（M3）, 2-oxo-5-OH-triptolide（M4）, respectively.Conclusion： The me-tabolite （M4） is reported for the first time.The main metabolites of triptolide are oxidates.