【摘要】 目的 建立一种检测定量干血斑中仑伐替尼浓度的液相色谱-串联质谱方法。方法 以仑伐替尼-[d₄]为内标，用乙腈/水（70/30）对干血斑样本进行萃取，用ProChromC₁₈反相色谱柱（2.1mm×100.0mm,3.0μm）进行分离，流动相为10mmol·L^-1乙酸铵水溶液和甲醇，梯度洗脱，流速为0.3mL·min^-1。在电喷雾离子源正离子模式下，用多反应监测模式检测仑伐替尼m/z427.1→370.0、338.0和仑伐替尼-[d₄]m/z431.1→370.0通道。对方法的选择性、标准曲线、残留、精密度与准确度、回收率、基质效应和稳定性进行了考察。结果 空白人全血干血斑基质中的内源性组分不会对检测产生影响。经优化后的预处理方法用乙腈/水（70/30）进行一步法提取，干血斑中仑伐替尼在10～250ng·mL^-1浓度内线性关系良好，干血斑中仑伐替尼在10～250ng·mL^-1浓度内线性关系良好，3个分析批的标准曲线方程分别为y=3.81×10^-2x+2.76×10^-2（r=0.9997）、y=2.0×10^-2x-4.87×10^-3（r=0.9999）、y=2.01×10^-2x-3.68×10^-3（r=0.9997），定量下限为10ng·mL^-1，批内、批间准确度相对误差在±15%范围内、精密度相对标准差（RSD）小于15%，无明显基质效，在高温45℃环境中可保持稳定至少7天。结论 本方法便捷、高效、准确，符合国际人用药品注册技术协调会M10《生物分析方法验证及样品分析》指导原则的要求，可用于干血斑样本中仑伐替尼浓度测定。更多还原

【Abstract】 Objective To develop a liquid chromatography-tandem mass spectrometry method for the detection of lenvatinib in quantitative dried blood spots.Methods Lenvatinom-[d₄] was used as the internal standard.The dried blood spot samples were extracted with acetonitrile/water（70/30） and separated on a ProChrom C18 reversed-phase column（2.1 mm × 100.0 mm,3.0 μm）.The mobile phase consisted of 10 mmol·L^-1 ammonium acetate solution and methanol with gradient elution.The flow rate was 0.3 mL·min^-1.The ionization was carried out under the electrospray ionization positive mode.Multiple reaction monitoring was used to detect the transitions of lenvatinib at m/z427.1→370.0 and 338.0,as well as lenvatinib-[d₄] at m/z 431.1→370.0.The specificity,standard curve,carryover,precision and accuracy,extraction recovery,matrix effect and stability of the method were investigated.Results Endogenous components in the dried blood spot matrix of blank human whole blood did not affect the determination.The optimized pretreatment employs a ostep extraction with acetonitrile/water（70/30）.Lenvatinib in dried blood spots demonstrated good linearity in the range of 10-250 ng·mL^-1.The standard curve equations from three analytical batches were y=3.81 × 10^-2x+2.76 ×10^-2（r=0.999 7）,y=2.0 × 10^-2x-4.87×10^-3（r=0.999 9）,y=2.01×10^-2x-3.68×10^-3（r=0.999 7）,respectively.The lower limit of quantification（LLOQ） was 10 ng·mL^-1.The intra-and inter-batch relative errors were within±15%,and relative standard deviation（RSD） were below 15%.There was no significant matrix effect,and lenvatinib dried blood spots sample remained stable for at least 7 days at a high temperature of 45 ℃.Conclusion The method is convenient,efficient and accurate and it is suitable for the requirements of The International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use M10 guideline " Bioanalytical Method Validation and Study Sample Analysis".It can be used for the determination of lenvatinib concentrations in dried blood spot samples.更多还原