同位素稀释-超高效液相色谱-串联质谱法测定人血浆中仑伐替尼的浓度

Determination of lenvatinib in human plasma by isotope dilution-ultra performance liquid chromatography-tandem mass spectrometry

目的建立同位素稀释-超高效液相色谱-串联质谱法测定人血浆中仑伐替尼的浓度。方法血浆样品用甲基叔丁醚进行液液萃取,取上清液后氮气吹干,50%甲醇水复溶后进样检测,同位素为内标用于定量,色谱柱为ZORBAX SB-C_(18)(2.1 mm×100.0 mm, 3.5μm),乙腈、0.1%甲酸水为流动相进行梯度洗脱,进样体积为3μL,用电喷雾离子源(ESI)、正离子、多反应监测模式。结果血浆中内源性物质不干扰仑伐替尼的测定,在1-500 ng·mL^(-1)线性关系良好,定量下限为1 ng·mL^(-1),批内、批间精密度RSD均小于15%,RE在-5.64%-4.40%,稳定性良好。结论本方法快速、准确、高效,适合用于人体仑伐替尼血浆药物浓度的测定。

Objective To establish an ultra-performance liquid chromatography-tandem mass spectrometry method with isotope dilution for the determination of lenvatinib concentration in human plasma. Methods The plasma samples were extracted by liquid-liquid extraction(LLE) with Methyl tert-butyl ether, The supernatant was blown dry with nitrogen, re-dissolved in 50% methanol-water, and then injected into the sample for detection. The chromatographic column was ZORBAX SB-C_(18)(2.1 mm×100.0 mm, 3.5 μm) with acetonitrile and 0.1% formic acid water as mobile phases for gradient elution, and the injection volume was 3 μL. Electrospray ion source(ESI), positive ion, and multi-response monitoring modes were used. Results The determination of lenvatinib was not interfered with by endogenous substances in plasma. The linearity was good in the range of 1-500 ng·mL^(-1), the lower limit of quantification was 1 ng·mL^(-1), the RSD of intra-and inter-batch precision was less than 15%, the RE was in the range of-5.64%-4.40%, and the stability was good under the given conditions. Conclusion This method is rapid, accurate, efficient, and suitable for the determination of lenvatinib plasma drug concentration in humans.