LC-MS/MS法同时测定人血浆中仑伐替尼和索拉非尼浓度

Determination of lenvatinib and sorafenib in human plasma by liquid chromatography-tandem mass spectrometry

目的建立一种同时测定人血浆中仑伐替尼和索拉非尼浓度的LC-MS/MS法,并应用于肝癌患者血浆中药物浓度测定。方法血浆样品经乙腈沉淀蛋白,用XSelect HSS XP(2.1 mm×100.0 mm,2.5μm)色谱柱进行分离,流动相为5 mmol·L^(-1)乙酸铵(含0.1%甲酸)-乙腈溶液,梯度洗脱,流速为0.3 mL·min^(-1)。用电喷雾离子源(electrospray ion source,ESI),正离子方式多反应监测模式。结果血浆中仑伐替尼和索拉非尼分别在0.2~1000.0 ng·mL^(-1)和5.0~5000.0 ng·mL^(-1)线性关系良好,日内、日间精密度RSD均小于15%。结论本方法符合生物样本分析要求,简便、高效、准确,可用于人血浆中仑伐替尼和索拉非尼浓度测定。

Objective To establish a rapid,specific,accurate liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of lenvatinib and sorafenib concentration in human plasma.Methods The plasma samples were precipitated by acetonitrile and separated on XSelect HSS XP column(2.1 mm×100.0 mm,2.5μm)with acetonitrile and 5 mmol·L^(-1) ammonium acetate(0.1%formic acid)at the flow rate of 0.3 mL·min^(-1).Electrospray ion source(ESI),positive ion,and multi-response monitoring modes were used.Results The linearity of lenvatinib and sorafenib in plasma was good within the range of 0.2-1000.0 ng·mL^(-1) and 5.0-5000.0 ng·mL^(-1).The RSD of both intra-day and inter-day studies were less than 15%.Conclusion This method is rapid,simple,accurate and suitable for the determination of lenvatinib and sorafenib plasma concentration monitoring in humans.