Abstract: A simple and rapid liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantitative determination of glycyrrhetic acid (GA), metabolite of glycyrrhizin and glycyrrhetate, in human plasma. GA and internal standard (IS, thiamphenicol) were separated on a C18 column by elution with acetonitrile-ammonium acetate solution (5 mmol/L) (70:30, v/v) after a simple liquid-liquid extraction with ethyl acetate. The flow rate was 0.8 mL/min. They were detected by tandem mass spectrometry in the negative ion multiple reaction monitoring (MRM) mode with ion transitions of m/z 469.3→355.3 for GA and m/z 354.1→185.0 for IS. The calibration curve was linear over GA concentration range of 0.5-500 ng/mL (r²>0.99), with intra- and inter- day precisions (RSD) of less than 7.1%, and mean extraction recovery of 74.3%. The method was used for the pharmacokinetic study of ammonium glycyrrhetate after its oral administration of a single dose of 75 mg ammonium glycyrrhetate tablet in humans. The main pharmacokinetic parameters of GA were as follows: AUC0-t (3457.26±1999.01) ng·h/mL; AUC0-∞ (3708.85±2428.36) ng·h/mL; MRT0-t (19.69±4.03) h; MRT0-∞ (22.83±8.45) h; t1/2Z (11.71±7.77) h; Tmax (13.40±4.84) h; CLz/F (29.17±19.82) L/h; Vz/F (487.38±518.07) L; Cmax (215.85±99.88) ng/mL.

Key words: Glycyrrhetic acid, Pharmacokinetics, LC-MS/MS, Ammonium glycyrrhetate