Perspectives of Quantitative GC-MS, LC-MS, and ICP-MS in the Clinical Medicine Science—The Role of Analytical Chemistry

Mass spectrometry (MS) is the only instrumental analytical technology that utilizes unique properties of matter, that is, its mass (<i>m</i>) and electrical charge (<i>z</i>). In the magnetic and/or electric fields of mass spectrometers, electrically charged native or chemically modified (millions) endogenous and (thousands) exogenous substances, the analytes, are separated according to their characteristic mass-to-charge ratio (<i>m</i>/<i>z</i>) values. Mass spectrometers coupled to gas chromatographs (GC) or liquid chromatographs (LC), the so-called hyphenated techniques, i.e., GC-MS and LC-MS, respectively, enable reliable determination of the concentration of analytes in complex biological samples such as plasma, serum, and urine. A particular technology is represented by inductively coupled plasma-mass spectrometry (ICP-MS), which is mainly used for the analysis of metal ions. The highest analytical accuracy is reached by using mass spectrometers with high mass resolution (HR) or by tandem mass spectrometers, as it can be realized with quadrupole-type instruments, such as GC-MS/MS and LC-MS/MS, in combination with stable-isotope labeled analytes that serve as internal standards, like a standard weight in scales. GC-MS belongs to the oldest and most advanced instrumental analytical technology. From the very beginning, GC-MS found broad application in basic and applied research sciences. GC-MS has played important roles in discovering biochemical pathways, exploring underlying mechanisms of disease, and establishing new evidence-based pharmacological therapy. In this article, we make an inventory of the use of instrumental mass spectrometry in the life sciences and attempt to provide a perspective study on the future of analytical mass spectrometry in clinical science, mainly focusing on GC-MS and LC-MS. We used information freely available in the scientific database PubMed (retrieved in August-November 2024). Specific search terms such as GC-MS (103,000 articles), LC-MS (113,000 articles), and ICP-MS (14,000 articles) were used in the Title/Abstract in the "PubMed Advanced Search Builder" including filters such as search period (1970-2024). In total, around 103,000 articles on GC-MS, 113,000 articles on LC-MS (113,000), and 14,000 articles on ICP-MS were found. In the period 1995-2023, the yearly publication rate accounted for 3042 for GC-MS articles and 3908 for LC-MS articles (LC-MS/GC-MS ratio, 1.3:1). Our study reveals that GC-MS/MS, LC-MS/MS, and their high-resolution variants are indispensable instrumentations in clinical science including clinical pharmacology, internal and forensic medicine, and doping control. Long-tradition manufacturers of analytical instruments continue to provide increasingly customer-friendly GC-MS and LC-MS apparatus, enabling fulfillment of current requirements and needs in the life sciences. Quantitative GC-MS and GC-MS/MS methods are expected to be used worldwide hand in hand with LC-MS/MS, with ICP-MS closing the gap left for metal ions. The significance of analytical chemistry in clinical science in academia and industry is essential.