Characterization of metabolites of ganoderic acids extract from Ganoderma lucidum in rats using UHPLC-MS/MS.

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Ganoderic acids, the primary active compound cluster in Ganoderma lucidum (Chinese name: Lingzhi), one of the most reputed herbal medicines, play a crucial role in its immunomodulatory, anti-inflammatory, and anticancer properties. To reveal the existence forms of this chemical cluster in rat, we characterized the herb-derived compounds following the oral administration of the ganoderic acids extract (GAE). Moreover, we conducted metabolite characterization for both ganoderic acid A (GAA) and ganoderic acid B (GAB) in parallel to explore the metabolic pathways for ganoderic acids. The biological samples, including bile, plasma, urine, and feces, were analyzed by UHPLC-MS/MS. After carefully summarizing the mass fragmentation rules of ganoderic acids, a total of thirteen and eleven were identified after oral administration of GAA and GAB, respectively, through converting MS/MS spectra into chemical structures. Oxidation, reduction, hydroxylation, glucuronidation and sulfation were proposed as the primary biotransformation routes, and thereof, hydroxylation accounted for more metabolite generation. Through applying mass fragmentation rules and the metabolic knowledge, 107 metabolites, in total, were identified as GAE-derived components in rat. The obtained results provided important information towards the therapeutical forms of GAE in vivo, and moreover, offered guidelines for metabolite characterization of, but not limited to, triterpenoids.