Institute of Laboratory Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Muenchen, Germany.
Anal Bioanal Chem. 2023 Sep;415(21):5049-5055. doi: 10.1007/s00216-023-04648-0. Epub 2023 Mar 25.
MS-based analytical methods now play an important role in medical laboratory analysis. Predominantly triple-stage mass spectrometry is used for the quantification of small molecule biomarkers and xenobiotics in blood and urine. The spectrum of applications ranges from completely in-house developed analytical methods, to industrially manufactured kit solutions used on generic equipment, to the first closed MS-based analysis systems. It is to be expected that the weights will shift in the coming years. Thus, operation and evaluation for most applications will remain very challenging and very different from the far more user-friendly and fully automated systems - mainly photometry-based - which are commonly used in clinical laboratories. General regulatory requirements for medical analysis differ significantly between countries globally. General requirements for in-house developed assay methods are valid in some countries, but concrete and methodology-specific rules for operation and quantification when using MS methods in the medical diagnostic laboratory are not applied. This differs significantly from other bio-analytical areas such as food monitoring, pharmaceutical research, or forensics, where legally binding, detailed rules exist in some cases, e.g., for substance identification. Internationally used relevant and helpful general standards with regard to mass spectrometric examination procedures in the clinical laboratory are in particular CLSI 62A and ISO 15189, while the IVDR in the EU primarily regulates the manufacture of diagnostic articles and not their application. In addition, from many years of application experience, some general advice can be recommended as rules that can contribute to robustness and patient safety in the clinical application of MS procedures; with emphasis on: reasonable method description, batch release, competence management, maintenance, and continuity management. This article also proposes some procedural basic requirements for the application of MS procedures in the clinical laboratory.
基于 MS 的分析方法目前在医学实验室分析中发挥着重要作用。主要使用三级串联质谱法来定量测定血液和尿液中的小分子生物标志物和外源性物质。应用范围从完全内部开发的分析方法，到工业制造的试剂盒解决方案，再到第一个封闭的基于 MS 的分析系统。可以预期，在未来几年，这种情况将会发生变化。因此，对于大多数应用，操作和评估仍然非常具有挑战性，而且与在临床实验室中常用的、更为用户友好和完全自动化的系统（主要基于光度法）非常不同。全球各国在医学分析方面的一般监管要求存在显著差异。一些国家对内部开发的检测方法有一般要求，但在医学诊断实验室中使用 MS 方法时，对于操作和定量的具体和方法特定的规则并未得到应用。这与其他生物分析领域（如食品监测、药物研究或法医学）存在显著差异，在这些领域，在某些情况下存在具有法律约束力的详细规则，例如物质鉴定。在临床实验室中，与质谱检查程序相关的国际上使用的相关和有用的一般标准主要是 CLSI 62A 和 ISO 15189，而欧盟的 IVDR 主要监管诊断制品的制造，而不是其应用。此外，从多年的应用经验中，可以推荐一些一般性建议作为规则，这些规则有助于提高 MS 程序在临床应用中的稳健性和患者安全性；重点是：合理的方法描述、批次放行、能力管理、维护和连续性管理。本文还提出了一些在临床实验室中应用 MS 程序的基本程序要求。
