HPLC-MS/MS法测定人血浆丙戊酸浓度的不确定度评定  

Uncertainty assessment of the determination of valproate concentration in human plasma by HPLC-MS/MS

作　　者：戴丽静 杨烨 刘威杨 孙秀佳[3] 温领华 温预关[1] DAI Lijing;YANG Ye;LIU Weiyang;SUN Xiujia;WEN Linghua;WEN Yuguan(The Affiliated Brain Hospital of Guangzhou Medical University,Guangzhou 510370,China;Guangzhou Yida Xinyao Chuangzhi Company Limited,Guangzhou 510700,China;Shanghai Key Laboratory of Psychotic Disorders/Shanghai Mental Health Center,School of Medicine,Shanghai Jiaotong University,Shanghai 200032,China)

机构地区：[1]广州医科大学附属脑科医院,广东广州510370 [2]广州医大新药创制有限公司,广东广州510700 [3]上海交通大学医学院附属精神卫生中心/上海市重性精神病重点实验室,上海200032

出　　处：《广东药科大学学报》2023年第3期32-37,共6页Journal of Guangdong Pharmaceutical University

基　　金：上海交通大学医工交叉研究基金(YG2021QN131);广东省医院药学研究基金资助项目(澳美基金2022A22);广东省药学会临床治疗精准用药专项基金(2023JZ14);广东省卫生计生适宜推广基金资助项目(粤卫办函[2018]326号)。

摘　　要：目的对HPLC-MS/MS法测定人血浆中丙戊酸浓度的不确定度进行评定与分析。方法测定人血浆中丙戊酸浓度,用A类评定评价重复性测量引入的不确定度,用B类评定对对照品称量、对照品纯度、溶液配制、含药血浆配制、提取回收率、基质效应、标准曲线拟合和仪器测定引入的不确定度进行评定,并计算合成和扩展不确定度。结果当P=95%置信概率(k=2)时,人血浆中低(1200 ng/mL)、中(12000 ng/mL)、高(75000 ng/mL)质量浓度丙戊酸的扩展不确定度分别为345.09、589.73、2789.74 ng/mL。结论方法准确度高,适用于丙戊酸的药动学研究和血药浓度监测。不确定度主要来源于标准曲线拟合、基质效应和提取回收率,低浓度时标准曲线拟合引入的不确定度值较中、高浓度的高。设定合理的线性范围、优化提取方式和色谱条件等可提高测定结果准确性。Objective To evaluate and analyze the uncertainty in the determination of valproate concentration in human plasma by HPLC-MS/MS.Methods The concentration of valproate in human plasma was determined.The uncertainty introduced by the measurement reproducibility was evaluated by Class A assessment,and the uncertainty introduced by the weighing and purity of reference substance,solution preparation,drug-containing plasma preparation,extraction recovery,matrix effect,standard curve fitting and instrument determination was evaluated by Class B assessment,and the synthetic and extended uncertainty was calculated.Results The extended uncertainty for low(1200 ng/mL),medium(12000 ng/mL),and high(75000 ng/mL)concentrations of valproate in human plasma was 345.09,589.73,and 2789.74 ng/mL,respectively,when confidence probability was P=95%(k=2).Conclusion The method of the study is accurate,which is suitable for the pharmacokinetic study and therapeutic drug monitoring of valproate.The sources of uncertainty are mainly calibration curve fitting,matrix effect and extraction recovery.The uncertainty values introduced by calibration curve fitting at low concentrations are higher than those at medium and high concentrations.Setting reasonable linear range,optimizing the extraction method and chromatographic conditions can improve the accuracy of the determination results.

关 键 词：丙戊酸 不确定度 HPLC-MS/MS 血浆药物浓度 

分 类 号：R969.1[医药卫生—药理学]