Pharmacokinetics of ginkgolide B-lyophilized nanoparticles after intravenous injection in rats using liquid chromatography-tandem mass spectrometry

RationaleGinkgolide B (GB) performs diverse pharmacological activities but has poor water solubility. The currently available GB injections have a short half-life and are lethal when injected rapidly. We prepared GB-lyophilized nanoparticles (GB-NPs) using a new nonsurfactant polysaccharide polymer, ZY-010, as its carrier to regulate the release of GB in vivo. Here, the pharmacokinetics (PK) of GB-NPs after intravenous injection in rats was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). MethodsThe samples were separated on an Agilent Eclipse XDB-C 18 column (2.1 x 50 mm, 1.85 mu m) maintained at 30 degrees 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 constructed, and the specificity, sensitivity, precision, and extraction recovery of LC-MS/MS analysis were assessed. The main PK parameters were analyzed using DAS (Drug And Statistics for Windows) software, version 2.0. ResultsThe retention time of GB and IS at elution was 2.77 and 4.75 min, respectively. An excellent linear response across the concentration range of 0.001-100 mu g/ml was achieved (r = 0.9997). The relative standard deviation value of precision was less than 10%. The total extraction recovery was above 80.76 +/- 2.08%. The main PK parameters for the GB-NPs were as follows: t(1/2) = 69.32 h, AUC((0 -> infinity)) = 188 312.97 +/- 143 312.41 mu g/L h, CL = 0.03 +/- 0.02 L/h/kg, and V = 0.09 +/- 0.05 L/kg. The t(1/2) of the GB-NPs was significantly longer than that of GB solution, and AUC((0 -> infinity)) of GB-NPs was about 1.4 times that of GB solution. The PK data demonstrated that the blood concentration of GB in rats conformed to a three-compartment model in both GB solution and GB-NPs. ConclusionA 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 compared with GB solution.