LC-MS/MS_法测定人血浆中培美曲塞浓度的不确定度评定

目的: 评定LC-MS/MS法测定人血浆中培美曲塞浓度的不确定度。 方法: 对培美曲塞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、液液萃取、仪器、标准曲线拟合等进行分析评定,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,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,最后根据各分量计算出合成不确定度并进行了扩展计算各变量的不确定度和合成不确定度,最终计算扩展不确定度。 结果: 人血浆中低(72.54 ng·mL^-1) 和中(725.39 ng·mL^-1)、浓度培美曲塞的扩展不确定度分别为6.18 ng·mL^-1和53.18 ng·mL^-1(P=95%,k=2)。 结论: LC-MS/MS法测定人血浆中培美曲塞浓度的不确定度主要由提取回收率(尤其是低浓度)、标准溶液和血浆样品制备处理及仪器允差引入。

Objective: To evaluate the uncertainty of pemetrexed determination in human plasma by LC-MS/MS. Method: The uncertainty caused by various factors in the whole process of determination,including repeatability,weighing,solution preparation,liquid-liquid extraction process,the apparatus and calibration fitting,was estimated.The uncertainty caused by random effects was evaluated with type A and others were with type B.The combined uncertainty was analyzed with all the components. Results: The expanded uncertainty for low(72.54 ng·mL^-1) and medium(725.39 ng·mL^-1 )level of pemetrexed was 6.18 and 53.18 ng·mL^-1,respectively(P=95%,k=2). Conclusion: The uncertainty of this method was mainly caused by extraction recovery(especially low level of sample),solution and plasma preparation,sample pretreatment and LC-MS/MS error.