UPLC-MS/MS法测定人脑脊液中去甲万古霉素含量不确定度评价

Uncertainty evaluation on the determination of norvancomycin in human cerebrospinal fluid by UPLC-MS/MS

目的评定UPLC-MS/MS测定人脑脊液中去甲万古霉素(NVCM)含量的不确定度。方法分析UPLCMS/MS法测定人脑脊液中去甲万古霉素含量的不确定度来源,计算不确定度并进行合成和扩展。结果去甲万古霉素在低浓度(3 mg·L^(-1))和高浓度(300 mg·L^(-1))的扩展不确定度分别为1.18、70.97 mg·L^(-1)(P=95%,k=2)。结论UPLC-MS/MS法测定人脑脊液中去甲万古霉素含量的不确定度在低含量时主要由曲线拟合、重复性和回收率引入。在高含量时主要由重复性,回收率和基质效应引入。本研究建立的脑脊液中去甲万古霉素含量测定方法,为该药物使用的安全性和有效性提供了有效的监管手段。

Objective To evaluate the uncertainty in norvancomycin(NVCM)determination in human cerebrospinal by UPLC-MS/MS.Methods The whole process during the NVCM determination was analyzed and the uncertainty sources were established,then the combined and expanded uncertainty were also evaluated.Results The expanded uncertainty with low(3 mg·L^(-1))and high(300 mg·L^(-1))levels of NVCM(P=95%,k=2)were 1.18 mg·L^(-1) and 70.97 mg·L^(-1),respectively.Conclusion The uncertainty in NVCM determination in human cerebrospinal by UPLC-MS/MS was mainly caused by curve fitting,repeatability and recovery for low concentrations and repeatability,matrix effect and recovery for high concentrations.The method for determining the content of NVCM in cerebrospinal fluid established by our research institute provides an effective regulatory means for the safety and effectiveness of the drug’s use.