Glucuronide-sulfate Diconjugate as a Novel Metabolite of Glycyrrhetic Acid in Rat Bile

Glucuronide-sulfate Diconjugate as a Novel Metabolite of Glycyrrhetic Acid in Rat Bile
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DOI:
10.2133/dmpk.23.175
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发表时间:
2008-01-01
影响因子:
2.1
通讯作者:
Jing, Ning
Jing, Ning
中科院分区:
医学4区
文献类型:
--
作者:
Jing, Jing;Ren, Weichao;Jing, Ning

文献摘要

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为研究甘草次酸(GA)在大鼠胆汁中的代谢产物,建立了一种用液相色谱-质谱联用(LC-MS)鉴定GA及其代谢产物的分析方法。静脉注射GA后收集大鼠胆汁。通过高效液相色谱(HPLC)分析,在254 nm处可在大鼠胆汁中检测到三个主要的GA相关峰。LC-MS光谱显示其质子化分子离子为m/z 727、647和551。此外,在LC-MS总离子色谱图(TIC)上也证实了这三种代谢产物存在于大鼠胆汁中。结合对β-葡萄糖醛酸酶消化和碱性条件的敏感性,将其分别鉴定为新型硫酸盐-葡萄糖醛酸苷双结合物和已知的单葡萄糖醛酸苷和硫酸盐结合物。
To study the metabolites of glycyrrhetic acid (GA) in rat bile, an analytical method was developed to identify GA and its metabolites by liquid chromatography mass spectrometry (LC-MS). Rat bile was collected after i.v. injection of GA. Three major GA-related peaks were detectable in rat bile by high-performance liquid chromatography (HPLC) analysis at 254 nm. LC-MS spectra showed their protonated molecular ions at m/z 727, 647, and 551. Furthermore, the three metabolites were also confirmed to exist in rat bile on LC-MS total ion chromatogram (TIC). Taken together with the susceptible nature to beta-glucuronidase digestion and alkaline conditions, they were identified to be a novel sulfate-glucuronide diconjugate and the known monoglucuronide and sulfate conjugate, respectively.