Metabolism profile of timosaponin B-II in urine after oral administration to rats by ultrahigh-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry
Metabolism profile of timosaponin B-II in urine after oral administration to rats by ultrahigh-performance liquid chromatography/quadrupole-time-of-flight mass spectrometry
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DOI：
10.1002/rcm.6299
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发表时间：
2012-09-15
影响因子：
2
通讯作者：
Chai, Yifeng
中科院分区：
文献类型：
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作者：
Liu, Zhirui;Zhu, Dongliang;Chai, Yifeng
知母皂苷B-II（TB-II）是从知母中分离的主要生物活性甾体苷类化合物之一。（Fam。百合科）。它被认为是一种潜在的先导化合物，可能进一步开发成为一种有前途的预防痴呆的新药。为了充分了解TB-II的作用机制，研究该化合物在体内的代谢特征是重要的。方法采用超高效液相色谱（UHPLC）/四极杆飞行时间质谱（QTOFMS）联用技术，对SD大鼠单次口服TB-II（500.4 mg.kg1）后尿液中TB-II的代谢进行研究。结果通过与母体药物的相对分子质量、保留时间和光谱图谱的比较，共鉴定出12个代谢产物。并对TB-II生物转化的可能代谢途径进行了研究。结论该化合物在大鼠体内的主要代谢过程为氧化、去糖基化和E环断裂。这是第一个报告的哺乳动物代谢研究知母皂苷，一个共同的成员类固醇苷，在大鼠尿中。版权所有（C）2012约翰威利父子有限公司
RATIONALE Timosaponin B-II (TB-II) is one of the major bioactive steroid glycosides isolated from Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has been regarded as a potential lead compound, which may be further developed into a promising new drug for preventing dementia. To fully understand the action mechanism of TB-II, it is important to study the metabolism profile of this compound in vivo. METHODS Herein, a rapid and sensitive method based on ultrahigh-performance liquid chromatography (UHPLC)/quadrupole-time-of-flight mass spectrometry (QTOFMS) was established to comprehensively investigate the metabolism of TB-II in SpragueDawley rat urine following oral administration of a single dose of TB-II at 500.4 mg.kg1. RESULTS A total of twelve metabolites were detected and identified by means of comparing molecular mass, retention time and spectral pattern of the analytes with those of the parent drug. A possible metabolic pathway on the biotransformation of TB-II was also investigated and proposed. CONCLUSIONS Oxidation, deglycosylation and E-ring cleavage were found to be the major metabolic processes of the compound in rat. It is the first report on a mammalian metabolism study of timosaponin, a common member of steroid glycosides, in rat urine. Copyright (C) 2012 John Wiley & Sons, Ltd.