In Vitro/In Vivo Metabolism of Ginsenoside Rg5 in Rat Using Ultra-Performance Liquid Chromatography/Quadrupole-Time-of-Flight Mass Spectrometry

Background: Ginsenoside Rg5 has been proved to have a wide range of pharmacological activities. However, the in vitro and in vivo metabolism pathways of ginsenosides are still unclear, which impedes the understanding of their in vivo fate. In this paper, the possible metabolic process of Rg5 was studied and the metabolites are identified. Methods: Samples from rat liver microsomes (RLMs) in vitro and from rat urine, plasma and feces in vivo were collected for analysis after oral administration of Rg5. A rapid analysis technique using ultra-performance liquid chromatography (UPLC)/quadrupole-time-of-flight mass spectrometry (QTOF-MS) was applied for detecting metabolites of Rg5 both in vitro and in vivo. Results: A feasible metabolic pathway was proposed and described for ginsenoside Rg5. A total of 17 metabolic products were detected in biological samples, including the RLMs (four), rat urine (two), feces (13) and plasma (four). Fifteen of them have never been reported before. Oxidation, deglycosylation, deoxidation, glucuronidation, demethylation and dehydration were found to be the major metabolic reactions of Rg5. Conclusions: The present study utilized a reliable and quick analytical tool to explore the metabolism of Rg5 in rats and provided significant insights into the understanding of the metabolic pathways of Rg5 in vitro and in vivo. The results could be used to not only evaluate the efficacy and safety of Rg5, but also identify potential active drug candidates from the metabolites.