Liquid chromatography-electrospray ionization mass spectrometry for metabolism and pharmacokinetic studies of ginsenoside Rg3

A sensitive and specific liquid chromatography (LC)-electrospray ionization (ESI) mass spectrometry (MS) method with quadrupole-time-of-flight detection was applied for the determination of ginsenoside Rg3 in rat plasma and its major metabolites in samples from in vitro metabolism studies. The biological samples were prepared by protein precipitation with methanol and the sample extracts were directly injected into a reversed-phase HPLC column with solvent gradient program. Pharmacokinetic study of Rg3 on rat gave a half-life of 14min after the ginsenoside was intravenously dosed. Metabolite identification and confirmation from the MS-MS and high-resolution MS analyses indicated that the short half-life might be due to the high rate of metabolic clearance of the ginsenoside under gastrointestinal conditions. Hydrolysis products of Rg3 such as ginsenoside Rh2 and protopanaxadiol were identified as the major metabolites from the incubation with 0.1M HCl, and a hydrated product of protopanaxadiol was detected as the metabolite with artificial gastric juice, while a monooxygenated metabolite was identified in the incubated samples with rat liver S9 fraction.