DETERMINATION OF GUANFU BASE A HYDROCHLORIDE IN PLASMA BY LC-MS METHOD AND ITS PHARMACOKINETICS IN DOGS

AIMTo establish an analytical method for determination of guanfu base A (GFA) concentration in plasma and to study its pharmacokinetic profile in dogs. METHODSSix dogs were given a 7.56 mg·kg^-1 dose intravenously. Blood samples were collected at various time-points after drug administration. Analytical method based on liquid chromatography-mass spectrometry (LC-MS) was established to determine the plasma concentration of GFA. Pharmacokinetic evaluation was carried out using the 3P87 program. RESULTSThe calibration curves were linear over the concentration range from 0.42 μg·mL^-1 to 21.2 μg·mL^-1 (γ=0.9994). The intra-day and inter-day precisions were generally good (<15%) at low, medium and high concentrations. The overall recovery of the analytes was more than 80%. Six dogs were given an iv dose of 7.56 mg·kg^-1 of GFA hydrochloride, an open three compartment model best described the concentration-time profiles for GFA. The half-lives for the rapid and slow distribution phase and terminal elimination phase (_t1/2π, _t1/2α and _t1/2β) were 0.07 h, 1.5 h, and 13.5 h, respectively. The total area under the plasma concentration-time curve (AUC), the volume of the central compartment (V_c), and plasma clearance (CL_s) were 61.43 μg·h·mL^-1, 0.37 L·kg^-1 and 0.14 L·kg^-1·h^-1, respectively. CONCLUSIONThe analytical method was shown to be sensitive, specific, rapid and reproducible, and was suitable for pharmacokinetic studies of GFA.