Pharmacokinetic analysis of α and β epimers of glycyrrhetinic acid in rat plasma: differences in singly and combined administrations

An HPLC method for the determination of 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid in rat plasma was established, which was used subsequently to determine the pharmacokinetic profiles of both epimers of glycyrrhetinic acid in rats.  α-glycyrrhetinic acid, β-glycyrrhetinic acid, and a mixture of α-glycyrrhetinic and β-glycyrrhetinic acids were administered to rats via gastric infusion.  Blood samples were collected at different time intervals and extracted by liquid-liquid extraction.  Separation was achieved by using a Kromasil C₁₈ column (150 mm × 4.6 mm, 5 µm) with the mobile phase composed of acetonitrile − 4 mmol·L⁻¹ ammonium acetate solution (46∶54, v/v) at a flow rate of 1.0 mL·min⁻¹, and the detection wavelength was set at 250 nm.  The pharmacokinetic parameters were calculated using the software DAS 2.0.  In a combined administration, the main pharmacokinetic parameters of β-glycyrrhetinic acid are significantly different from that of α-glycyrrhetinic acid (P < 0.05), while no significant difference was obtained when administrated individually.  Compared to the single administration, significant differences (P < 0.05) on the values of AUC_0−t and AUC_0−∞ of β-glycyrrhetinic acid were observed when this chemical was administrated together with α-glycyrrhetinic acid.  In contrast, the pharmacokinetic parameters of α-glycyrrhetinic acid were not affected even under the co-administration.  Here, a sensitive, specific, rapid and reproducible HPLC method was developed for the pharmacokinetic studies of α-glycyrrhetinic acid and β-glycyrrhetinic acid in rat plasma.