LC-MS/MS法同时测定血浆中布南色林和N-去乙基布南色林浓度的不确定度评价

Evaluations of the Measurement Uncertainty for the Simultaneous Determination of Blonanserin and N-desethyl Blonanserin in Plasma Using LC-MS/MS

目的对LC-MS/MS同时测定血浆中布南色林以及N-去乙基布南色林浓度的不确定度进行评价和分析。方法采用A类评定对重复测量引入的不确定度进行评价,采用B类评定评价对标准品称量、标准溶液制备、血浆标准样本制备、液液萃取法提取血浆样本、液质联用仪测定以及标准曲线拟合过程中引入的不确定度进行评价,综合A类评定和B类评定结果,计算LC-MS/MS法同时测定血浆中布南色林以及N-去乙基布南色林浓度的合成和扩展不确定度。结果当置信概率为95%时,血浆中低(20 ng·L^-1)、中(400 ng·L^-1)、高(3000 ng·L^-1)浓度布南色林的扩展不确定度分别为1.301,19.646,181.682 ng·L^-1,血浆中低(20 ng·L^-1)、中(100 ng·L^-1)、高(500 ng·L^-1)浓度N-去乙基布南色林的扩展不确定度分别为4.436,19.925,121.231 ng·L^-1。结论LC-MS/MS测定血浆布南色林以及N-去乙基布南色林浓度时,优化提取过程、提高定量下限和选择合适的线性回归权重因子,是提高浓度测量结果准确性的有效方法。

OBJECTIVE To evaluate the measurement uncertainty for the determination of blonanserin and N-desethyl blonanserin in human plasma using LC-MS/MS.METHODS The uncertainty that caused by repeat measurement was evaluated as type A uncertainty,while those caused by the weighing of standard substances,preparations of stock solutions and calibrators,plasma sample extraction using liquid-liquid extraction,LC-MS/MS determination and calibration curve regression were analyzed as type B uncertainty.The expanded and combined uncertainties were then combined and calculated.RESULTS The expanded uncertainties for blonanserin at low(20 ng·L^-1),middle(400 ng·L^-1)and high(3000 ng·L^-1)concentrations were 1.301,19.646,181.682 ng·L-1,respectively(P=95%).The expanded uncertainties for N-desethyl blonanserin at low(20 ng·L-1),middle(100 ng·L^-1)and high(500 ng·L^-1)concentrations were 4.436,19.925,121.231 ng·L^-1,respectively(P=95%).CONCLUSION The measurement uncertainty for the simultaneous determination of blonanserin and N-desethyl blonanserin could be reduced by optimizating extraction procedure,increasing lower limit of quantification and weighting factor selection.