肌酸和胍基乙酸纯度标准物质定值研究及其不确定度评估  

Development of Purity Certified Reference Materials for Creatine and Guanidinoacetic Acid and Their Uncertainty Evaluation

作　　者：刘粮泽 刘若祎 屈子裕 易可可 叶子弘 俞晓平 江游[1,2] 戴新华 方向[1,2] 谢洁 LIU Liangze;LIU Ruoyi;QU Ziyu;YI Keke;YE Zihong;YU Xiaoping;JIANG You;DAI Xinhua;FANG Xiang;XIE Jie(Technology Innovation Center of Mass Spectrometry for State Market Regulation,Beijing 100029,China;Center for Advanced Measurement Science,National Institute of Metrology,Beijing 100029,China;China Jiliang University,College of Life Sciences,Hang Zhou 310000,China;China Jiliang University,College of Metrology Measurement and Instrument,Hang Zhou 310000,China)

机构地区：[1]中国计量科学研究院前沿计量科学中心,北京100029 [2]国家市场监管技术创新中心(质谱),北京100029 [3]中国计量大学生命科学学院,杭州310000 [4]中国计量大学计量测试与仪器学院,杭州310000

出　　处：《计量科学与技术》2025年第2期61-72,共12页Metrology Science and Technology

基　　金：国家重点研发计划项目(2021YFC2401100);中国计量科学研究院基本科研业务费(AKY1934)。

摘　　要：采用质量平衡法与定量核磁法两种不同原理的方法,对肌酸和胍基乙酸标准物质候选物的纯度进行定值研究,并系统评估了标准物质研制过程中引入的不确定度。采用质谱法、红外光谱法和核磁共振氢谱法对标物原料进行了定性分析;用卡尔费休库仑滴定法测定水分含量,用离子色谱法对不挥发性杂质进行定量,用顶空气相色谱法测定挥发性杂质的含量,采用高效液相色谱、液相色谱-串联质谱法对与主成分结构类似杂质进行了分析;采用高效液相色谱法进行均匀性检验和稳定性考察。同时系统分析与评估了标准物质研制过程中称量、定值、均匀性和稳定性等引入的不确定度,肌酸和胍基乙酸的纯度定值结果分别为99.30%、99.30%,相对扩展不确定度为0.16%、0.14%(k=2)。研制的肌酸和胍基乙酸纯度标准物质,可为临床上肌酸缺乏症的诊断提供溯源依据。The purity of candidate reference materials for creatine and guanidinoacetic acid was investigated using two methods based on different principles:mass balance method and quantitative NMR method.The uncertainties introduced during the development of these reference materials were systematically evaluated.Mass spectrometry,infrared spectroscopy,and nuclear magnetic resonance hydrogen spectroscopy were used for qualitative analysis of the raw materials.Karl Fischer coulometric titration was employed to determine moisture content,ion chromatography for quantification of non-volatile impurities,and headspace gas chromatography for determination of volatile impurity content.Highperformance liquid chromatography(HPLC)and liquid chromatography-tandem mass spectrometry(LC-MS/MS)were used to analyze impurities with structures similar to the main components.HPLC was employed for homogeneity testing and stability studies.The uncertainties introduced during the development process,including those from weighing,value assignment,homogeneity,and stability,were systematically analyzed and evaluated.The purity values for creatine and guanidinoacetic acid were determined to be 99.30%and 99.30%,respectively,with relative expanded uncertainties of 0.16%and 0.14%(k=2).The developed purity reference materials for creatine and guanidinoacetic acid can provide a traceable basis for the clinical diagnosis of creatine deficiency.

关 键 词：计量学 肌酸 胍基乙酸 标准物质 质量平衡法 定量核磁法 不确定度 

分 类 号：TB99[一般工业技术—计量学]