Pharmacokinetics of Ginkgolide B Lyophilized Nanoparticles Following Intravenous Injection in Rats by Using LC-MS/MS.

Abstract

Ginkgolide B (GB) has diverse pharmacological activities but poor water-solubility. The currently available GB injections have a short half-life and are lethal when injected fast. We prepared GB lyophilized nanoparticles (GB-NPs) with a new non-surfactant polysaccharide polymer, ZY-010, as its carrier to regulate the release of GB in vivo. Here, the pharmacokinetics of GB-NPs following intravenous injection in rats was performed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The samples were separated on an Agilent Eclipse XDB-C 18 column (2.1×50 mm, 1.85 μm) maintained at 30°C. The MS/MS transitions of GB and glibenclamide as the internal standard (IS) were set at m/z 423.1→367.1 and m/z 492.1→367.0, respectively. The standard curve of GB content was established, and the specificity, sensitivity, precision and extraction recovery of LC-MS/MS analysis were assessed. The main pharmacokinetic parameters were analyzed using software DAS ver 2.0. The retention time (RT) of GB and IS eluted at 2.77 and 4.75 min, respectively. An excellent linear response across the concentration range of 0.001-100 μg/mL was achieved (r=0.9997). The relative standard deviation (RSD) value of precision was less than 10%. The total extraction recovery was above (80.76 ± 2.08)%. The main pharmacokinetic parameters for the GB-NPs were as follows: t1/2 =69.32 h, AUC(0→∞) = (188312.97 ± 143312.41) μg/L·h, CL= (0.03 ± 0.02) L/h/kg and V= (0.09 ± 0.05) L/kg. The t1/2 of the GB-NPs was significantly longer than that of GB solution, and AUC(0→∞) of GB-NPs was about 1.4 times of that of GB solution. The pharmacokinetic data demonstrated that the blood concentration of GB in rats conformed to a three-compartment model in both GB solution and GB-NPs. A rapid and accurate LC-MS/MS method was established for the determination of GB-NPs in rats. GB-NPs exhibited a sustained-release behavior in vivo comparing with GB solution.