干旱区生态环境知识资源中心

A highly sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of glycyrrhizin (GL) and its active metabolite, glycyrrhetinic acid (GA), from human plasma was validated and applied to a human pharmacokinetic study. The analytes were extracted from human plasma using an Oasis MAX cartridge and chromatographic separation was performed on an Inertsil ODS-3 column. The detection was performed using an API 4000 mass spectrometer operating in the positive electrospray ionization mode. Selected ion monitoring transitions of m/z 823453 for GL and m/z 471149 for GA were obtained. The response was a linear function of concentration over the ranges of 0.5-200ng/mL for GL and 2-800ng/mL for GA (both R-2>0.998). Using this method, the pharmacokinetics of GL after single oral administration of a clinical dose (75mg) to six healthy male Japanese volunteers were evaluated. GL was detected in the plasma of all subjects and the average peak concentration was 24.8 +/- 12.0ng/mL. In contrast, peak concentration of GA was 200.3 +/- 60.3ng/mL, i.e. similar to 8-fold higher than that of GL. This is the first report clarifying pharmacokinetic profiles of GL and GA simultaneously at a therapeutic oral dose of a GL preparation.