Pharmacokinetics and bioavailability study of ginsenoside Rk1 in rat by liquid chromatography/electrospray ionization tandem mass spectrometry.
BIOMEDICAL CHROMATOGRAPHY(2019)
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 x 2.1 mm, 1.8 mu m). 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 similar to 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.
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Key words
bioavailability,ginsenoside Rk1,LC-MS,MS,pharmacokinetics
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