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Hyphenated mass spectrometry (MS) has evolved into a very powerful analytical technique of high sensitivity and specificity. It is used to analyze a very wide spectrum of analytes in classical and alternative matrices. The presented paper will provide an overview of the current state-of-the-art of hyphenated MS applications in clinical toxicology primarily based on review articles indexed in PubMed (1990 to April 2023). A general overview of matrices, sample preparation, analytical systems, detection modes, and validation and quality control is given. Moreover, selected applications are discussed. A more widespread use of hyphenated MS techniques, especially in systematic toxicological analysis and drugs of abuse testing, would help overcome limitations of immunoassay-based screening strategies. This is currently hampered by high instrument cost, qualification requirements for personnel, and less favorable turnaround times, which could be overcome by more user-friendly, ideally fully automated MS instruments. This would help making hyphenated MS-based analysis available in more laboratories and expanding analysis to a large number of organic drugs, poisons, and/or metabolites. Even the most recent novel psychoactive substances (NPS) could be presumptively identified by high-resolution MS methods, their likely presence be communicated to treating physicians, and be confirmed later on.

Current state-of-the-art approaches for mass spectrometry in clinical toxicology: an overview