Study on pharmacokinetics of pazopanib in rats / 药学实践杂志

ABSTRACT

Objective To develop a UPLC-MS method for the determination of pazopanib in rat plasma, and study the pharmacokinetics of pazopanib in rats.Methods The effective UPLC MS/MS separation of the examined compounds was applied on an Acquity BEH C18 column with a gradient mobile phase system.AB Sciex QTRAP 5500 triple quadruple mass spectrometer equipped with an electrospray ionization (ESI) interface was used for mass spectrometric detection.The MRM transitions of m/z 438.3→357.2 and m/z 285.2→193.1 were used to quantify for pazopanib and ISTD, respectively;6 rats were given 80 mg/kg pazopanib intragastric administration.Blood samples were collected from the tail vein at different point after administration.The concentration of pazopanib in plasma was detected by the UPLC-MS methods.The pharmacokinetics parameters were analyzed by DAS program.Results Pazopanib and ISTD were eluted at 1.10 and 1.37 min respectively.Excellent liner relationship was obtained from the range of 0.25 μg/ml to 40.00 μg/ml (r=0.999 2).The intra-day RSD were 6.17%, 2.73% and 2.54% and inter-day RSD were 7.56%, 5.98% and 2.84% respectively at three concentrations (0.50, 10.00, 30.00 μg/ml), the recoveries were (78.4±4.8)%, (85.9±3.5)% and (81.1±4.2)% respectively, the Matrix effect were (106.7±5.3) %, (101.3±6.7) % and (97.6±4.4) % respectively at three concentrations (0.50, 10.00, 30.00 μg/ml);6 rats were given 80 mg/kg pazopanib intra-gastric administration.The main pharmacokinetics parameters of pazopanib were as following cmax (20.22±1.95) μg/ml,tmax (1.75±0.76) h,t1/2 (7.35±2.31) h,AUC0-t (213.16±39.92) μg·h/L,AUC0-∞ (215.79±39.84) μg·h/L,Vd (4.10±1.78) L/kg,CL (0.38±0.07) L/h.Conclusion The method was simple, rapid, accurately,which could be used to determine the pazopanib concentration in rat plasma and study on its pharmacokinetics.Pazopanib was fitted to the first-order elimination kinetics in rats.