Plasma and brain pharmacokinetics of ganoderic acid A in rats determined by a developed UFLC-MS/MS method

- Development of a UFLC-MS/MS method to determine GAA in plasma and ventricular CSF.
- First investigation of PK properties of GAA in plasma and ventricular CSF of rats.
- GAA could be rapidly absorbed into the body and penetrate into the brain.

Ganoderic acid A (GAA), an active triterpenoid of the traditional Chinese herbal medicine Lingzhi, has been reported to exhibit antinociceptive, antioxidative, and anti-cancer activities. The present study aims to establish a sensitive and rapid UPLC-MS/MS method for studying the plasma and brain pharmacokinetics of GAA in rats. The analytes were separated on a C18 column eluted with a gradient mobile phase consisting of acetonitrile and 0.1% aqueous formic acid at 0.3 mL/min. The eluate was monitored by a mass detector using an MRM (m/z, 515.3-285.1) model in negative electrospray ionization. The calibration curve showed good linearity (r2 > 0.99), with limits of detection and quantification of 0.25 and 2.00 nmol/L, respectively. The intra- and inter-day precision and accuracy were less than 9.99% and ranged from 97.45% to 114.62%, respectively. The extraction recovery from plasma was between 92.89% and 98.87%. GAA was found to be stable in treated samples at room temperature (22 °C) for 12 h and in plasma at −20 °C for 7 d. The developed method was successfully applied to a pharmacokinetic study of GAA in rats. GAA could be rapidly absorbed into the circulation (Tmax, 0.15 h) and eliminated relatively slowly (t1/2, 2.46 h) after orally dosing, and could also be detected in the brain lateral ventricle (Tmax, 0.25 h and t1/2, 1.40 h) after intravenously dosing. The absolute oral bioavailability and brain permeability of GAA were estimated to be 8.68% and 2.96%, respectively.