Identification and quantitative determination of a major circulating metabolite of gambogic acid in human.
Gambogic acid (GA), a promising anticancer candidate, is a polyprenylated xanthone abundant in the resin of Garcinia morella and Garcinia hanburyi. The major circulating metabolite of GA in human, 10-hydroxygambogic acid (10-OHGA), was identified by comparison of the retention time and mass spectra with those of reference standard using liquid chromatography-tandem mass spectrometry. The reference standard of 10-OHGA was isolated from bile samples of rats after intravenous injection of GA injection, and its structure was confirmed by NMR. Then, a selective and sensitive method was developed for the quantitative determination of this metabolite in human plasma. After liquid-liquid extraction by ethyl acetate, the analyte and the internal standard were separated on a Sepax HPC18 column (100 mm x 2.1 mm i.d., 3.0 microm) with a mobile phase of 10mM ammonium acetate water solution containing 0.1% formic acid-acetonitrile (20:80, v/v). The detection was performed on a single quadrupole mass spectrometer equipped with electrospray ionization (ESI) source. The calibration curve was linear over the range of 3-2000 ng/mL for 10-OHGA. The developed quantification method can now be used for the pharmacokinetic and pharmacological studies of 10-OHGA after intravenous infusion of GA injection in human.
Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
Jing
J
Yang
Li
L
Ding
Shaohong
S
Jin
Xiaoxue
X
Liu
Wenyuan
W
Liu
Zhenzhong
Z
Wang
D000704:Analysis of Variance; D000818:Animals; D001646:Bile / Q000737:chemistry* / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D044004:Xanthones / Q000097:blood* / Q000378:metabolism
C550001:10-hydroxygambogic acid; D044004:Xanthones; C052659:gambogic acid