LC-MS/MS法测定血浆中色瑞替尼浓度的不确定度评定

Uncertainty evaluation of determination of ceritinib concentration in plasma by LC-MS/MS

目的:评定高效液相色谱质谱(LC-MS/MS)法测定血浆中色瑞替尼浓度的不确定度。方法:本研究对色瑞替尼浓度测定过程中各影响因素,包括测定精密度、称量、标准溶液的配制、含药血浆的配制、血浆样品预处理、仪器、标准曲线拟合等进行分析评定,采用A类评定程序评价了分析过程中随机效应引起的不确定度,采用B类评定程序评价了分析过程的其他因素引起的不确定度,根据各分量计算得到扩展不确定度和合成不确定度。结果:血浆中10,100和800 ng·m L-1色瑞替尼的扩展不确定度分别为13.122,13.397和125.654 ng·m L-1(P=95%,k=2)。结论:LC-MS/MS法测定血浆中色瑞替尼浓度的不确定度主要由标准曲线拟合引入。

Objective： To evaluate the uncertainty of determination of ceritinib in plasma by LC-MS/MS method. Methods： The uncertainties caused by various factors in the whole process of determination,such as repeatability,weighing,solution preparation,sample preparation process,the apparatus and calibration fitting,were comprehensively estimated. The uncertainty caused by random effects and others was elucidated in terms of type A and type B,respectively. The expanded uncertainties and combined uncertainty were analyzed with all the components. Results： The expanded uncertainties for ceritinib concentrations of 10,100 and 800 ng·m L-1 were13. 122,13. 397 and 125. 654 ng·m L-1,respectively（P = 95%,k = 2）. Conclusion： The uncertainty of this LC-MS/MS method is mainly caused by calibration curve fitting.