Identification of 20(S)-protopanaxatriol metabolites in rats by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance spectroscopy
Identification of 20(S)-protopanaxatriol metabolites in rats by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance spectroscopy
复制标题
DOI：
10.1016/j.jpba.2013.09.031
复制
发表时间：
2014-01-25
影响因子：
3.4
通讯作者：
Wang, Zhengtao
中科院分区：
文献类型：
--
作者：
He, Chunyong;Zhou, Dandan;Wang, Zhengtao
20（S）-原人参三醇（PPT）是人参皂苷的苷元之一，具有抗心肌缺血损伤的作用。然而，关于PPT代谢的研究很少报道。本研究首次采用超高效液相色谱-电喷雾电离四极杆飞行时间串联质谱（UPLC-Q/TOF-MS）和核磁共振（NMR）光谱法研究口服PPT后的体内代谢。根据MS数据、MS 2数据和色谱保留时间的特征鉴定代谢物的结构。共发现22种代谢物，包括17种相和5种II相代谢物，并通过与PPT的质谱图谱比较初步鉴定。合成了两个新的单氧代谢产物：（205，24 S）-环氧-达玛烷-3，6，12，25-四醇和（20 S，24 R）-环氧-达玛烷-3，6，12，25-四醇，并通过核磁共振谱进行了结构表征。据此首次提出了PPT的代谢途径。结果表明，（1）（Delta（（24，25）处的双键氧化形成24，25-环氧化物，然后重排产生20，24-氧化物形式;（2）C-26/27处的乙烯基甲基形成相应的羧酸是主要的代谢途径。首次证明II相代谢途径由葡萄糖醛酸化和半胱氨酸结合组成。本研究为PPT的代谢提供了有价值的新信息，这对于了解PPT及其相应的皂苷的安全性和有效性是不可或缺的。(C)2013爱思唯尔有限公司版权所有。
20(S)-Protopanaxatriol (PPT), one of the aglycones of ginsenosides, has been shown to exert cardioprotective effects against myocardial ischemic injury. However, studies on PPT metabolism have rarely been reported. This study is the first to investigate the in vivo metabolism of PPT following oral administration by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) and nuclear magnetic resonance (NMR) spectroscopy. The structures of the metabolites were identified based on the characteristics of their MS data, MS2 data, and chromatographic retention times. A total of 22 metabolites, including 17 phase land 5 phase ll metabolites, were found and tentatively identified by comparing their mass spectrometry profiles with those of PPT. Two new monooxygenation metabolites, (205,24S)-epoxy-dammarane3,6,12,25-tetraol and (20S,24R)-epoxy-dammarane-3,6,12,25-tetraol, were chemicallly synthesized and unambiguously characterized according to the NMR spectroscopic data. The metabolic pathways of PPT were proposed accordingly for the first time. Results revealed that oxidation of (1) double bonds at (Delta((24,25))) to form 24,25-epoxides, followed by rearrangement to yield 20,24-oxide forms; and (2) vinyl-methyl at C-26/27 to form corresponding carboxylic acid were the predominant metabolic pathways. Phase II metabolic pathways were proven for the first time to consist of glucuronidation and cysteine conjugation. This study provides valuable and new information on the metabolism of PPT, which is indispensable for understanding the safety and efficacy of PPT, as well as its corresponding ginsenosides. (C) 2013 Elsevier B.V. All rights reserved.