Quantitative Determination of Ginsenoside Rg1 in Rat Plasma by Ultra-high Performance Liquid Chromatography-tandem Mass Spectrometry (UHPLC-MS/MS) and its Application in a Pharmacokinetics and Bioavailability Study

Background: Ginsenoside Rg1 (Rg1) is the main active compound of ginseng herbs. Objective: The aim of this study is to develop a rapid, selective and sensitive ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the levels of Rg1 in rat plasma and investigate the pharmacokinetics and bioavailability of Rg1 in rats. Methods: Chromatographic separation was achieved on an UHPLC-MS/MS system with an UPLC BEH C18 column using an elution gradient of a mixture of acetonitrile and water (with 0.1% formic acid). The analytes were quantitatively determined by negative-mode electrospray tandem MS. Results: The linearity of the calibration curve was from 2 to 1,000 ng/mL (r ≥ 0.9956), and the lower limit of quantification was 2 ng/mL. The inter-day and intra-day precision were both lower than 12.0%, and the accuracy ranged from 90.6 to 109.7%. The recovery of the targets was higher than 87.0%, and the matrix effect at three different analyte concentrations were from 89.0 to 97.2%. The bioavailability of Rg1 was only 6.1% due to a poor oral absorption. Conclusion: This new quantitative method was found to be sensitive, rapid and selective, and was successfully used to study the pharmacokinetics of Rg1 after intravenous and oral administration in rats.