In Vivo Metabolism Study of Timosaponin BIII in Rat Using HPLC-QTOF-MS/MS
In Vivo Metabolism Study of Timosaponin BIII in Rat Using HPLC-QTOF-MS/MS
复制标题
DOI：
10.1007/s10337-014-2681-1
复制
发表时间：
2014-05
期刊：
影响因子：
1.7
通讯作者：
Dandan Li;Rui Xue;Zhi-xiong Li;Ming-cang Chen;Weixin Jiang;Chenggang Huang
中科院分区：
文献类型：
--
作者：
Dandan Li;Rui Xue;Zhi-xiong Li;Ming-cang Chen;Weixin Jiang;Chenggang Huang
知母皂苷BIII是从银莲花中分离得到的甾体皂苷类化合物，近年来被证实具有多种药理活性，成为一种具有良好开发前景的天然活性化合物。在本研究中，一个简单而快速的方法，使用高效液相色谱/四极杆飞行时间质谱法测定知母皂苷BIII及其代谢产物的结构后，灌胃给药300 mg kg−1的大鼠。通过与母体化合物的分子量（ΔM）、保留时间和光谱图的变化进行比较，在尿液中检测并鉴定了9种代谢物，在血浆中检测并鉴定了8种代谢物，在脑中检测并鉴定了4种代谢物。初步鉴定了9个代谢产物的结构，分别为知母皂苷BII（M1）、TBII的羟基化代谢产物（M2）、TBIII的羟基化代谢产物（M3）、TBII的羟基化代谢产物（M4）、TBII的羟基化代谢产物（M5）和TBIII的羟基化代谢产物（M6）（M3和M4）、TBIII的去糖基化和单氧化产物（M5）、TBII的去糖基化产物（M6）、知母皂苷AIII（M8）、知母皂苷AIII的异构体（M7和M9）。
Timosaponin BIII, as one of the steroid saponins isolated fromAnemarrhena asphodeloidesBge., was proved to have many pharmacological activities in recent years and became a natural active compound with good development prospect. In the present study, a simple and rapid method using high-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry was developed for the determination of the structures of timosaponin BIII and its metabolites in rats after administrating intragastrically at 300 mg kg−1. By comparing their changes in molecular masses (ΔM), retention times and spectral patterns with those of the parent compound, nine metabolites were detected and identified in urine, and eight in plasma as well as four in brain. It is also indicated that the deglycosylation and oxidation reactions were the main metabolic pathways in the biotransformation of timosaponin BIII in vivo and the structures of the nine metabolites were identified and proposed to be timosaponin BII(M1), the hydroxylated metabolite of TBII(M2), the hydroxylated metabolites of TBIII(M3 and M4), deglycosylation and monooxygenation product of TBIII(M5), the deglycosylation product of TBII(M6), timosaponin AIII(M8), the isomers of timosaponin AIII(M7 and M9).