Rules for mass spectrometry applications in the clinical laboratory.

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.