Simultaneous determination of 18alpha- and 18beta-glycyrrhetic acid in human plasma by LC-ESI-MS and its application to pharmacokinetics.
A highly sensitive and selective LC-ESI-MS was developed, validated for the simultaneous determination of 18alpha-glycyrrhetic acid (alpha-GA) and 18beta-glycyrrhetic acid (beta-GA) for pharmacokinetic studies in healthy subjects. Sample preparation was performed by liquid-liquid extraction with ethyl acetate and the separations were achieved using a C(18) column with the mobile phase composed of 10 mmol/L ammonium acetate solution-methanol-acetonitrile (40:36:24, v/v/v) at a flow rate of 1 mL/min. The internal standard was honokiol and the epimers were quantified using a single quadrupole mass spectrometer employing ESI in the negative ion mode. The separation factor, alpha, was 1.512 for alpha- and beta-GA. The standard curves were linear for both epimers with coefficients of determination (r >or= 0.9998) over the concentration range of 1-150 ng/mL. The precision and accuracy were <or= 4.33 and <or= 6.57%, respectively. The mean plasma extraction recoveries were 82.23 +/- 1.91 and 84.29 +/- 2.09% for alpha-GA and beta-GA, respectively. The assay was successfully applied to evaluation of the pharmacokinetic properties of alpha-GA and beta-GA from 19 volunteers who had received oral administration of diammonium glycyrrhizinate capsules. The initial data suggest that glycyrrhizin metabolizes to glycyrrhetic acid fairly slowly and the elimination of alpha-GA is slower than that of beta-GA.
Zou
Qiaogen
Q
College of Life Science and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing, People's Republic of China.
Wei
Ping
P
Li
Jing
J
Ge
Zheng-Xiang
ZX
Ouyang
Pingkai
P
D000893:Anti-Inflammatory Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D006034:Glycyrrhetinic Acid / Q000031:analogs & derivatives / Q000097:blood* / Q000493:pharmacokinetics; D006801:Humans; D015394:Molecular Structure; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D000893:Anti-Inflammatory Agents; C119129:18alpha-glycyrrhetinic acid; D006034:Glycyrrhetinic Acid