摘要
目的建立大鼠血浆中检测帕唑帕尼的超高效液相色谱-质谱(UPLC-MS)的方法,研究帕唑帕尼在大鼠体内的药动学过程。方法大鼠血浆样品用乙腈沉淀后检测。采用Acquity U-HPLC BEH C18柱为分离柱,流动相采用乙腈-0.1%甲酸体系,梯度洗脱;采用AB Sciex QTRAP 5500三重四级杆质谱仪(电喷雾离子源)进行质谱检测,帕唑帕尼和内标地西泮采用多反应监测(MRM)的方法检测,帕唑帕尼和内标地西泮(ISTD)的MRM分别为m/z 438.3→357.2和m/z285.2→193.1;雄性SD大鼠6只,灌胃给予80mg/kg帕唑帕尼,在给药前和给药后的不同时间点于大鼠尾静脉取血。用建立的方法测定血浆中帕唑帕尼的浓度。用DAS 3.0计算主要药动学参数。结果大鼠血浆中帕唑帕尼浓度在0.25~40.00μg/ml范围内线性关系良好(r=0.999 2);低、中、高3个质量浓度(0.50、10.00、30.00μg/ml)的日内精密度RSD分别为6.17%、2.73%和2.54%,日间精密度RSD分别为7.56%、5.98%和2.84%,回收率分别为(78.4±4.8)%、(85.9±3.5)%和(81.1±4.2)%,基质效应分别为(106.7±5.3)%、(101.3±6.7)%和(97.6±4.4)%;血浆帕唑帕尼的主要药动学参数:峰值浓度cmax为(20.22±1.95)μg/ml,达峰时间tmax为(1.75±0.76)h,半衰期t1/2为(7.35±2.31)h,药-时曲线下面积AUC0-t为(213.16±39.92)μg·h/L,AUC0-∞为(215.79±39.84)μg·h/L,表观分布容积Vd为(4.10±1.78)L/kg,清除率CL为(0.38±0.07)L/h。用房室模型拟合,帕唑帕尼在大鼠体内呈一级消除的二室模型。结论本研究建立用UPLC-MS检测大鼠血浆帕唑帕尼的方法,专属性高,分离完全,检测时间短;适合帕唑帕尼的药动学和药物相互作用研究。
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→357.2and m/z 285.2→193.1were used to quantify for pazopanib and ISTD,respectively;6rats were given 80mg/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 0.25μg/ml to 40.00μg/ml(r=0.999 2).The intra-day RSD were6.17%,2.73% and 2.54% and inter-day RSD were 7.56%,5.98% and 2.84% respectively at three concentrations(0.50,10.00,30.00μg/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(0.50,10.00,30.00μg/ml);6rats were given 80mg/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.
出处
《药学实践杂志》
CAS
2017年第4期346-349,共4页
Journal of Pharmaceutical Practice