液相色谱-串联质谱在生物样品定量测定中存在的不准确因素分析和对策

发布时间：2018-09-04 14:12

【摘要】：液相色谱-串联质谱(LC-MS/MS)技术是目前生物样本中小分子成分及部分蛋白和多肽定量分析中最广泛使用的技术。与LC相比,LC-MS/MS具有分析速度快、分辨率和灵敏度高、方法开发简单、可多组分同时测定等优点。在方法学开发过程中,分析者的主要操作一般是遵循法规的要求逐项进行方法学验证。但是,基于LC-MS/MS定量分析的原理,即使所建立的分析方法完全按照法规的要求进行了验证,在一些方面如不加以注意,也可能带来定量不准确的问题,即所谓的陷阱(生物分析风险)。笔者归纳了使用LC-MS/MS进行生物样本分析中常见的与不准确有关的问题,尤其是一些不能通过常规方法学验证发现的问题,包括:生物样本处理过程的逆转化、基质效应、源内裂解以及质荷比相近离子的干扰等。为了解决以上问题,除加强质量体系建设和进行严格的分析方法验证外,还可以采取去除基质效率高的样本处理方法、加强色谱分离、选择合适的离子反应、使用给药后样本进行方法学验证等措施。
[Abstract]:Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is the most widely used technique in the quantitative analysis of small molecular components and some proteins and peptides in biological samples. Compared with LC, LC-MS / MS / MS has the advantages of high analytical speed, high resolution and sensitivity, simple development and multicomponent simultaneous determination. In the process of methodology development, the main operation of the analyzer is to carry out the methodological verification one by one in accordance with the requirements of laws and regulations. However, based on the principle of quantitative analysis of LC-MS/MS, even if the established analytical methods are verified in accordance with the requirements of laws and regulations, if not paid attention to in some aspects, it may also lead to the problem of inaccurate quantitative analysis. This is called a trap (biological analysis risk). In this paper, we summarize some common problems related to inaccuracy in biological sample analysis using LC-MS/MS, especially some problems that can not be found by conventional methodology, including: reversal of biological sample processing process, matrix effect, The cleavage in the source and the interference of similar ions in mass charge ratio. In order to solve the above problems, in addition to strengthening the quality system construction and strict analysis method verification, we can also take the sample treatment method with high matrix removal efficiency, enhance chromatographic separation, and select the appropriate ion reaction. After administration of the drug samples were used for methodology verification and other measures.
【作者单位】：北京大学第一医院临床药理研究所;国家食品药品监督管理总局药品审评中心;中国科学院上海药物研究所药物代谢研究中心;
【分类号】：R927;O657.63

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