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Identification of the metabolites of rhapontigenin in rat and human by ultra‐high‐performance liquid chromatography—high‐resolution mass spectrometry
Author(s) -
An Jingzhi,
Yang Jie,
Wei Yuan,
Liu Yunsi,
Song Yan,
Zhang Zuzhuo,
Pan Ying
Publication year - 2021
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.9180
Subject(s) - chemistry , glucuronidation , sulfation , chromatography , orbitrap , mass spectrometry , metabolic pathway , demethylation , electrospray ionization , metabolite , microsome , glucuronide , urine , high performance liquid chromatography , metabolism , biochemistry , gene expression , dna methylation , gene , enzyme
Rationale Rhapontigenin, a stilbene compound isolated from the medicinal plant of rhubarb rhizomes, has shown a variety of biological activities. The purpose of this study was to identify and characterize the metabolites of rhapontigenin in rat liver microsomes, hepatocytes, urine, and human liver microsomes and hepatocytes. Methods The samples were analyzed by ultra‐high‐performance liquid chromatography combined with electrospray ionization quadrupole/orbitrap high‐resolution mass spectrometry (UPLC‐Q/Orbitrap‐HRMS). The structures of the metabolites were interpreted by MS, MS/MS data, and elemental compositions. Results A total of 11 metabolites were detected and tentatively identified. M1, identified as piceatannol, was unambiguously identified using reference standard. Our results suggested that rhapontigenin was metabolized through the following pathways: (a) demethylation to produce piceatannol (M1), which further underwent oxidation to form ortho ‐quinone intermediate. This intermediate was reactive and conjugated with GSH (M10 and M11), which were further converted into N ‐acetyl‐cysteine and excreted in urine. M1 also underwent sulfation (M8) and glucuronidation (M5); (b) direct sulfation, forming M6 and M7; and (c) direct glucuronidation to form M2, M3, and M4. Glucuronidation was a major metabolic pathway in hepatocytes and urine. Conclusions The current study provides an overview of the metabolism of rhapontigenin, which is of great importance for us to understand the disposition of this compound.