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.