Metabolic profiles of Ribociclib in rat and human liver microsomes by using liquid chromatography combined with electrospray ionization high resolution mass spectrometry.

In this study, metabolic profiles of Ribociclib were investigated by using rat and human liver microsomes. Metabolites were structurally identified by liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI-HR-MS) operated in positive ion mode. The metabolites were characterized by accurate masses, MS2 spectra and retention times. With rat and human liver microsomes, a total of 10 metabolites were detected and further identified. There were no human specific metabolites were detected. The metabolic pathways of Ribociclib referred to oxygenation, demethylation, and dealkylation. Most importantly, two GSH adducts were identified in human liver microsomes fortified with GSH. The formation of the GSH adducts was hypothesized to be through the oxidation of electron-rich 1,4-benzenediamine to 1, 4-diiminoquinone intermediate, which is highly reactive and can be trapped by GSH to form stable metabolites. The current study provides an overview of the metabolic profiles of Ribociclib in vitro, which would be of great help for us to understand the efficacy and toxicity of this drug. PMID: 31899811 [PubMed - as supplied by publisher]
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Tags: Biomed Chromatogr Source Type: research