Structural elucidation of in vivo metabolites of isobavachalcone in rat by LC–ESI-MSn and LC–NMR

• A novel LC–ESI–MSn method is used to investigate the in vivo metabolism of isobavachalcone.
• The fragmentation pathways of isobavachalcone were elucidated using ESI-MSn in both positive and negative ion mode.
• Five phase I metabolites are biotransformed via hydroxylation, reduction, cyclization and oxidative cleavage.
• Ten phase II metabolites are mainly identified as the glucuronide conjugates and sulfated conjugate.
• These findings are reported for the first time and contributed further understanding of the intermediate processes and metabolic mechanism.

Isobavachalcone (IBC) is a prenylated chalcone and belongs to the class of flavonoids, which is an active component isolated from Psoralea corylifolia L. IBC showed a range of significant pharmacological activities, including antibacterial, anticancer, anti-reverse transcriptase and antioxidant actions. In this research, the mass spectral fragmentation pattern of IBC was investigated to predict the in vivo metabolites, and five phase I metabolites and ten phase II metabolites of IBC in rat bile were elucidated and identified after oral administration using novel LC–ESI-MSn and LC–NMR method. The molecular structures of these metabolites were proposed on the basis of the characteristics of their precursor ions, product ions, MS/MS fragment behaviors and chromatographic retention time. The phase I metabolites were mainly biotransformed via the hydroxylation, reduction, cyclization and oxidative cleavage reactions. The phase II metabolites were mainly identified as the glucuronide conjugates and sulfated conjugates. All these findings were reported for the first time and would contribute to a further understanding of the in vivo intermediate processes and metabolic mechanism of isobavachalcone and its analogs.

The proposed metabolic pathways of isobavachalcone in rat.Figure optionsDownload as PowerPoint slide