In vitro studies on the metabolism of saikogenins and the detection of their metabolites in authentic biosamples

Publication date: Available online 30 April 2019Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Yunwen Xue, Jingjing Liu, Ruijia Fu, Lei Gao, Xuping Yang, Zunjian Zhang, Rui SongAbstractSaikosaponins are the representative bioactive ingredient in the Radix Bupleuri. Previous studies have reported that saikosaponins are prone to losing their glycones and being converted to corresponding prosaikogenins and saikogenins by intestinal bacteria. However, the microsomal cytochrome P450-mediated metabolism of these deglycosylated metabolites is still unknown. This research performed in vitro studies of five saikogenins in rat and human liver microsomes. High-performance liquid chromatography coupled with a hybrid ion trap and time-of-flight mass spectrometry (HPLC-IT/TOF-MS) was employed to identify the metabolites. To confirm the metabolites detected in vitro, plasma and feces obtained from rats administrating several saikogenins were also analyzed by high-performance liquid chromatography with triple-quadrupole mass spectrometry (HPLC-QqQ-MS). The in vitro metabolic stability of saikogenins was ranked as follows: SGF＞SGG＞SGE＞SGA＞SGD. A total of 71 metabolites generated by hydroxylation, carboxylation, and dehydrogenation, as well as combinations of these steps, were identified by accurate mass measurement and MSn fragmentation behavior. Among eight metabolic pathways, monohydroxylation or carboxylation was the major metabolic pathway both in vitro and in...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research