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目的建立人血浆中索拉菲尼浓度测定的HPLC-MS/MS方法。方法人血浆样品用乙腈-沉淀蛋白后,色谱柱:Eclipse Plus C18(2.1 mm×100 mm,3.5μm),流动相:乙腈∶10 mmol·L~(-1)醋酸铵溶液(均含0.05%甲酸)=80∶20,流速:0.25 m L·min~(-1)。用电喷雾离子化源,正离子方式,多反应监测扫描方式进行监测。考察该方法的专属性、标准曲线和定量下限、精密度与回收率、基质效应以及稳定性。结果血浆中索拉菲尼的线性范围为0.02~10.00μg·m L~(-1)(r=0.997 1),定量下限为0.02μg·m L~(-1);质控样品的准确度在95.01%~104.86%;日内、日间RSD均小于15%;提取回收率为82.08%~89.72%,无明显基质效应。质控样品室温放置8 h、处理后自动进样器4℃放置12 h,反复冻融3次,于-80℃环境中放置20 d后准确度在91.78%~106.19%,RSD在4.31%~9.73%。结论本方法快速、灵敏、准确,专属性强,重复性好,适用于人血浆中索拉菲尼浓度的测定。
Objective To establish an HPLC-MS / MS method for determination of sorafenib in human plasma. METHODS: Human plasma samples were eluted with acetonitrile-precipitated protein. The chromatographic column was eluted with Eclipse Plus C18 (2.1 mm × 100 mm, 3.5 μm) and acetonitrile: 10 mmol·L -1 ammonium acetate solution (both containing 0.05% Formic acid) = 80:20, flow rate: 0.25 m L · min -1. Electrospray ionization source, positive ion mode, multi-reaction monitoring scanning method for monitoring. The specificity, standard curve and quantification limit, precision and recovery, matrix effect and stability of this method were investigated. Results The linear range of sorafenib in plasma was 0.02-10.00 μg · m L -1 (r = 0.997 1) and the lower limit of quantification was 0.02 μg · m L -1. The accuracy of the quality control samples Between 95.01% and 104.86%. The RSDs of intra-day and inter-day were all less than 15%. The extraction recoveries ranged from 82.08% to 89.72% with no obvious matrix effects. The quality control samples were placed at room temperature for 8 h, and the autosampler was placed at 4 ° C for 12 h after treatment. The samples were frozen and thawed repeatedly for 3 times, and the accuracy was 91.78% -106.19% and the RSD was 4.31% 9.73%. Conclusion The method is rapid, sensitive, accurate, specific and reproducible. It is suitable for the determination of sorafenib in human plasma.