Forensic toxicologists traditionally “screen” biological specimens for the presence of individual drugs, drug classes, or their metabolites to rule out the presence of analytes that are detected by these techniques or to indicate when further testing is warranted. The presence of analytes that are presumptively detected by these screening techniques are “confirmed” by a second analytical technique that is based upon one or more different chemical principles than the screening technique. This approach has generally been accepted as adequate proof that an analyte has been “identified” in the biological specimen. However, this approach may not adequately account for the wide array of techniques and instrumentation in forensic toxicology laboratories and the fact that each technique offers a range of identification potential. Others have attempted to make the identification process more objective through a pointbased system. [1-3] An American National Standard was recently published to do the same. [4] The document sets minimum criteria – based on a point system – for analyte identification during forensic toxicology testing. It allows laboratories to evaluate each analytical technique to determine if their testing regimen is sufficient to meet or exceed a minimum point threshold for identification. This talk will discuss the point-based system for forensic toxicology, with particular focus on the use of mass spectrometry techniques [5] and will demonstrate how the standard may be used in a laboratory setting.

While mass spectrometry-based medical diagnostics are increasingly supported by industrial supplies (kit solutions, fully automated systems), most applications in clinical laboratories still fall into the laboratory developed test (LDT) category. These are important because they address innovative analytes and thus optimize care for rare diseases in particular. Nevertheless, the particular risks that may be associated with the use of LDTs in patient care must be considered. In the EU, a key legislative requirement in this context is the In Vitro Diagnostics Regulation (IVDR). It should be noted that the scope of the IVDR, according to Article 2, is primarily in rem articles manufactured in connection with LDTs in healthcare facilities [1]. The IVDR is not sufficient for ensuring fully controlled processes in the safety-critical operation of medical laboratories. To ensure safe processes in the overall laboratory, ISO standard 15189 has proven very effective over the past decade, but it does not provide any specifications that relate specifically to the use of mass spectrometry. For this purpose, a description of MS-based LDT as precise as possible seems to be particularly important for the long-term stability of methods [2]. CLSI Standard C62 is now widely used as a basis for the initial validation of clinical LS-MS methods, while it should be noted that the validation standards of EMA and FDA are not intended for diagnostic applications. Compared to the initial validation of a clinical MS method, sustainable quality assurance by very specific rules for the release of measurement batches and single results in long-term operation is rather underestimated, but should be considered as dynamic validation as an essential part of a respective method and addressed in detail [3].

High resolution mass spectrometry (HRMS/MS) coupled to gas and particularly liquid chromatography is increasingly used in environmental sciences for target analysis, screening of suspected compounds such as pesticides or pharmaceuticals with high consumption as well as non-target analysis of unknown compounds, e.g. industrial chemicals. It facilitates to extend the range of monitored compounds in various environmental matrices from legacy to emerging contaminants [1]. For target analysis with reference standards, specific requirements using HRMS/MS confirmation have been proposed in the EU (EC 2002/657/EC and SANTE/12682/2019) and in a modified version applied to more than 2000 compounds in wastewater [2]. For non-target screening including suspect screening, harmonization of protocols and minimum quality requirements is currently discussed in the community to provide high quality data useful also for regulatory processes. The confidence of identification is increasingly communicated using a five level system [3].The first draft of a national guideline for non-target screening is available in Germany (German Chemical Society), with a specific focus on surface water monitoring. In Europe, the NORMAN network aims to provide a more general guideline based on the experiences gained through different collaborative trials and other activities for water, indoor dust and biota. In the US, the working group BP4NTA for benchmarking and publications for non-targeted analysis was formed and shares information in publications and on the web. In this presentation, common HRMS quality assurance practice in the environmental science community will be presented and challenges especially for non-target screening discussed using illustrative examples.