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本研究建立并验证了一种简单、快速且灵敏的液质联用方法,用于测定裸鼠血浆中阿西替尼的浓度,并将其应用于药物动力学实验。血浆样品采用含有内标物埃罗替尼的乙腈进行蛋白沉淀处理。色谱分离过程使用C18反相色谱柱(50 mm×2 mm,5μm),以简单溶剂系统甲醇–水(60:40,v/v)作流动相,流速0.4 mL/min。质谱检测过程使用三重四极杆串联质谱,以电喷雾正离子模式、质谱多反应监测技术对待测物阿西替尼和内标埃罗替尼进行检测。标准曲线的线性范围为1至1000 ng/mL(r>0.99),其最低浓度为定量下限。方法日间日内精密度为7.7%–12.0%,准确度介于88.6%与110.4%之间。该方法成功应用于雌性nu/nu裸鼠口服给予120 mg/kg阿西替尼的临床前药物动力学研究,采用一级吸收一室模型描述其药动学行为。
This study established and validated a simple, rapid and sensitive LC-MS method for the determination of the concentration of axitinib in nude mice plasma and its application in pharmacokinetic experiments. Plasma samples were treated with acetonitrile containing the internal standard erlotinib for protein precipitation. The chromatographic separation was performed on a C18 reversed-phase column (50 mm × 2 mm, 5 μm) using a simple solvent system of methanol-water (60:40, v / v) as mobile phase at a flow rate of 0.4 mL / min. Mass spectrometry detection process using triple quadrupole tandem mass spectrometry, electrospray positive ion mode, mass spectrometry and multi-reaction monitoring of the test substance axitinib and the internal standard of erlotinib for testing. The calibration curve has a linear range of 1 to 1000 ng / mL (r> 0.99) with the lowest concentration being the lower limit of quantitation. Methods Intra-day precision was 7.7% -12.0% with an accuracy of between 88.6% and 110.4%. The method was successfully applied to the preclinical pharmacokinetics study of 120 mg / kg axitinib in female nu / nu nude mice. The first-order absorption model was used to describe the pharmacokinetics.