[#2017-07] Reishi Cao, Fang-Ruie et al. Plasma and brain pharmacokinetics of ganodric acid A in rats determined by a developed UFLC-MS MS method

Ganoderic acid A (GAA), an active triterpenoid of the traditional Chinese herbal medicine Lingzhi, hasbeen reported to exhibit antinociceptive, antioxidative, and anti-cancer activities. The present study aimsto establish a sensitive and rapid UPLC–MS/MS method for studying the plasma and brain pharmacoki-netics of GAA in rats. The analytes were separated on a C18 column eluted with a gradient mobile phaseconsisting of acetonitrile and 0.1% aqueous formic acid at 0.3 mL/min. The eluate was monitored by amass detector using an MRM (m/z, 515.3-285.1) model in negative electrospray ionization. The calibra-tion curve showed good linearity (r2> 0.99), with limits of detection and quantification of 0.25 and 2.00nmol/L, respectively. The intra- and inter-day precision and accuracy were less than 9.99% and rangedfrom 97.45% to 114.62%, respectively. The extraction recovery from plasma was between 92.89% and98.87%. GAA was found to be stable in treated samples at room temperature (22◦C) for 12 h and in plasmaat −20◦C for 7 d. The developed method was successfully applied to a pharmacokinetic study of GAA inrats. 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 andt1/2, 1.40 h) after intravenously dosing. The absolute oral bioavailability and brain permeability of GAAwere estimated to be 8.68% and 2.96%, respectively.