Pharmacokinetics and bioavailability study of ginsenoside Rk1 in rat by liquid chromatography/electrospray ionization tandem mass spectrometry

Abstract

Ginsenoside Rk1 (Rk1) exhibited various potent biological activities. However, its pharmacokinetic profile in vivo remains unclear. In the present study, a simple and sensitive liquid chromatography tandem mass spectrometry method was developed and validated for determination of Rk1 in rat plasma and applied in a pharmacokinetic study. The sample was precipitated with acetonitrile and separated on a Zorbax Eclipse XDB C18 column (50 × 2.1 mm, 1.8 μm). The mobile phase was composed of 0.1% formic acid in water and acetonitrile at a flow rate of 0.4 mL/min. Rk1 and internal standard (ginsenoside Rg3) were quantitatively monitored with precursor‐to‐product ion transitions of m/z 765.4 → 441.5 and m/z 783.5 → 621.4, respectively. The assay was linear over the concentration range of 5–1000 ng/mL (r > 0.99) with the LLOQ of 5 ng/mL. Other parameters including intra‐ and inter‐day precision and accuracy, extraction recovery and matrix effect were within the acceptable limits. The analyte was stable under the tested storage conditions. The validated method has been successfully applied to a pharmacokinetic study of Rk1 in rat plasma after intravenous (5 mg/kg) and oral (25 mg/kg, 50 mg/kg) administration. After oral administration, Rk1 could be detected in blood at 30 min and reached the highest concentration at 4.29~4.57 h. Our results demonstrated that Rk1 showed low clearance, moderate half‐life (3.09–3.40 h) and low bioavailability (2.87–4.23%). The study will provide information for the further application of Rk1.

Pharmacokinetic studies of ginsenosides Rk1 and Rg5 in rats by UFLC–MS/MS

“…The typical equations were y = 0.00891059x + 0.00183307 (R 2 > 0.995) and y = 0.00882761x + 0.00183307 (R 2 > 0.991) for ginsenosides Rk1 and Rg5, respectively, where y and x are peak area ratios and concentration ratios of analytes to IS. The LLOQs of ginsenosides Rk1 and Rg5 were 2 ng/ml (S/N >10), which was lower than previously established method with the LLOQ of 5 ng/ml for ginsenoside Rk1 (Li, Li, Zhang, Fan, & Liu, 2019).…”

“…Compared with the extensive literature on the pharmacological activities, few works have been done on the pharmacokinetics, which is crucial for drug discovery and development (Jones et al, 2015). Although a pharmacokinetic study of ginsenoside Rk1 has been done (Li, Li, Zhang, Fan, & Liu, 2019), pharmacokinetic information on ginsenoside Rg5 is absent. In addition, pharmacokinetic studies of ginsenosides Rk1 and Rg5 could be helpful to clarify the relationship between pharmacokinetics and the structural preference of ginsenosides.…”

The Anti-Tumor Effect and Underlying Apoptotic Mechanism of Ginsenoside Rk1 and Rg5 in Human Liver Cancer Cells

“…In addition, the bioavailability of major ginsenosides is very low. The minor ginsenosides such as G-Rk1 and G-Rg5, which are transformed from the major ginsenosides through a deglycosylation, have higher bioavailability and absorption [ 41 ]. In this study, we confirmed the anti-tumor effect of G-Rk1 and G-Rg5 on highly metastatic liver cancer cell line, MHCC-97H.…”

Ginsenoside Rg3 Ameliorates DSS-Induced Colitis by Inhibiting NLRP3 Inflammasome Activation and Regulating Microbial Homeostasis

“…9 As a transformation metabolite of gut microbiota, Gin Rg3 is found to be easily absorbable, which is different from other ginsenosides such as Rd and Rk. 10 However, we still know little about the immunomodulatory effect of Gin Rg3, a key metabolite in the UC model. Therefore, it is necessary to clarify the role and mechanism of Gin Rg3 in UC as soon as possible to explore the pharmacological effects of ginseng in UC.…”