Pharmacokinetic study on glycyrrhetinic acid in rats ig administrated by Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle Decoction / 中草药

ABSTRACT

Objective: To establish an LC-MS/MS method for determination of glycyrrhetinic acid (GA) in plasma after ig administration of Glycyrrhizae Radix et Rhizoma Praeparata Cum Melle (Zhigancao) Decoction in rats in vivo. Methods: Treating plasma with ethyl acetate protein precipitation and taking reseveratrol was used as the internal standard (IS), the residues were analyzed with LC-MS/MS system (Agilent ORBAX SB-C18 RP column, 50 mm x 2.1 mm, 1.8 μm) with the mobile phase consisted of acetonitrile-water (80 20, 0.2% formic acid), flow-rate of 0.2 mL/min, and column temperature of 30 °C. Agilent 6410 triple quad mass spectrometer system with an electrospray ionization (ESI) source and negative ion mode was used as the detector in this study. Multi-reaction monitoring (MRM) was used to detect GA by using ion combinations of m/z 469.4→425.4 for GA and 227.1→143.0 for IS. Results: The calibration curve showed good linear regression (R2 = 0.997 1) within measurement ranges (33.4-8 560.0 ng/mL). Both the intra- and inter-day precision and variation RSD were less than 10%. The average recovery rates at low, medium, and high concentrations of GA were 75.3%, 78.2%, and 78.5%, respectively. Under these conditions, the pharmacokinetic parameters of GA in plasma of rats after ig administration of Zhigancao Decoction were t max (8.00 ± 1.13) h, Cmax (811.02 ± 300.25) ng/mL, and AUC0.24 (11 439.21 ± 3 367.36) ng/mL·h. Conclusion: The method provides a sensitive, accurate, precise, and reliable analytical procedure for detecting GA in rat plasma and studying its pharmacokinetics.