Identification of bilobetin metabolites, in vivo and in vitro, based on an efficient ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry strategy.

Bilobetin, a natural compound extracted from Ginkgo biloba, has various pharmacological activities such as anti-oxidation, anti-cancer, anti-bacterial, anti-fungal, anti-inflammatory, anti-viral, and promoting osteoblast differentiation. However, few studies have been conducted and there are no reports on its metabolites owing to its low content in nature. In addition, it has been reported to have potential liver and kidney toxicity. Therefore, this study aimed to identify the metabolites of bilobetin in vitro and in vivo. Bilobetin was incubated with liver microsomes to determine metabolites in vitro, and faeces and urine were collected after oral administration to rats to determine metabolites in vivo. After the samples were processed, they were measured using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. As a result, a total of 21 and 9 metabolites were detected in vivo and in vitro, respectively. Demethylation, demethylation and loss of water, demethylation and hydrogenation, demethylation and glycine conjugation, oxidation, methylation, oxidation and methylation, and hydrogenation were the main metabolic pathways. This study is the first to identify the metabolites of bilobetin and provides a theoretical foundation for the safe use of bilobetin in clinical application and the development of new drugs. This article is protected by copyright. All rights reserved.