Simultaneous determination and pharmacokinetic study of gambogic acid and gambogenic acid in rat plasma after oral administration of Garcinia hanburyi extracts by LC‐MS/MS

Abstract

Gambogic acid and gambogenic acid are two major bioactive components of Garcinia hanburyi, and play a pivotal role in biologic activity. In this study, a specific and sensitive liquid chromatography-tandem mass spectrometry was developed and validated for simultaneous determination of gambogic acid and gambogenic acid in rat plasma. Chromatographic separation was achieved on a C18 column using an isocratic elution with methanol-10 m m ammonium acetate buffer-acetic acid (90:10:0.1, v/v/v) as the mobile phase. The detection was performed on a triple-quadrupole tandem mass spectrometer equipped with electrospray positive ionization using multiple reaction monitoring modes. The transitions monitored were m/z 629.3 [M + H](+) → 573.2 for gambogic acid, m/z 631.2 [M + H](+) → 507.2 for gambogenic acid and m/z 444.2 [M + NH4 ](+) → 83.1 for IS. Linear calibration curves were obtained in the concentration range of 2.00-1000 ng/mL for gambogic acid and 0.500-250 ng/mL for gambogenic acid. The lower limits of quantification of gambogic acid and gambogenic acid in rat plasma were 2.00 and 0.500 ng/mL, respectively. The intra- and inter-day precision (RSD) values were <11.7% and accuracy (RE) was -10.6-12.4% at three QC levels for both analytes. The assay was successfully applied to evaluate pharmacokinetics behavior in rats after oral administration of Garcinia hanburyi extracts.

MCL-1 inhibition in cancer treatment

“… 47 GA also exerts moderate efficacy in H22 xenograft tumors with only 45% tumor inhibition after 2 mg/kg ip dosing. 48 …”

Nanosuspensions as delivery system for gambogenic acid: characterization and in vitro/in vivo evaluation

“…Previous studies have confirmed that GNA has a broad spectrum anti-tumor effect in breast cancer cell line, lung cancer cells and other cancer cells (Fan et al, 2013;Zhou et al, 2013;Wang et al, 2014). However, the poor solubility, short biological half-life and excessive vascular irritation of GNA hindered its clinical application (Hua et al, 2015). In order to enhance delivery efficiency and bioavailability of GNA, we have used nanotechnology and successfully prepared PEGylated non-ionic surfactant vesicles and solid lipid nanoparticles of GNA in previous researches (Huang et al, 2013;Lin et al, 2013).…”

UHPLC‐MS method for determination of gambogic acid and application to bioavailability, pharmacokinetics, excretion and tissue distribution in rats

“…Ding et al (2007) developed a liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry with single ion monitoring method for the determination of GA in human plasma with LLOQ of 31 ng/mL. Recently, Hua et al (2014) quantified GA and gambogenic acid in rat plasma after oral administration of Garcinia hanburyi extracts by LC-MS. Bioavailability (BA), excretion and tissue distribution for GA were not reported in the above paper. These methods might be sensitive enough for the quantification of GA in biosamples after intravenous injection.…”

“…These methods might be sensitive enough for the quantification of GA in biosamples after intravenous injection. Recently, Hua et al (2014) quantified GA and gambogenic acid in rat plasma after oral administration of Garcinia hanburyi extracts by LC-MS. Bioavailability (BA), excretion and tissue distribution for GA were not reported in the above paper.…”