**4. Clinical proteomics**

*Mass Spectrometry in Life Sciences and Clinical Laboratory*

measuring a large of compounds.

part of possible applications.

specific analytical approach.

**3. Separation approaches**

performing analyses and tests has significantly changed. In the 1950's additional developments were made and, in 1957 and 1959, respectively, the autoanalyzer, which is the precursor to the modern analytical systems, and the first RIA (immunoassay) for analysis of insulin were introduced. The introduction of RIA, which is still widely used, for insulin has significantly improved and changed the art of

The introduction of the mass spectrometry (MS) into the clinical laboratory had had the same revolutionary impact as the previously mentioned methods. A brief search for "mass spectrometry" and "clinical" from 1950 until 1970 results with only 9 publications! During the next 20 years, until 1990, the number of publications referring to the use of MS for different analyses in clinical laboratory jumped to 798! From the early 1990's until today, the steep rise of MS methods and approaches for analyses in clinical laboratory has steeply raised with more than

The significant rise in use of different MS approaches for clinical analyses correlates with improvements in ionization technologies, miniaturization of separation systems, notably of chromatographic systems (HPLC) [1], the significant and exciting improvements in sample preparation even of a single cell [2], and bioinformatic analysis. The mass spectrometry is applied for both "classical" clinical laboratory analyses and for analyzing samples for personalized and precision medicine. Undoubtly, the approaches and methods describe in current book are only a small

In clinical laboratories, the analysis of clinical samples and monitoring levels of active compounds and their metabolites in e.g. patients' blood and urine samples are the main application fields. It is possible to perform specific detection of target analytes by applying MRM/SRM (multiple-reaction monitoring/selected-reaction monitoring) or SIM (single-ion monitoring) thus significantly enhancing the selectivity and sensitivity of the analytical method and provide targeted and highly

Analytes of interest in complex biological samples must be separated prior to mass spectrometric detection and analysis and chromatography is the most widely used separation method for biological samples prior to MS. A number of Companies, e.g. Chromsystems (https://www.chromsystems.com/), ThermoFisher Scientific (https://www.thermofisher.com/at/en/home/clinical/diagnostic-testing/ clinical-chemistry-drug-toxicology-testing/therapeutic-drug-monitoring.html), Biocrates (https://biocrates.com/) or BioRad (www.bio-rad.com) developed analytical systems for a broad range of analyses of important clinical parameters. Integrated HPLC–MS clinical systems were also developed but they never really did find broad acceptance. Sciex introduced the Topaz® system (https://www. businesswire.com/news/home/20170731005050/en/First-Fully-Integrated-LC-MS-System-for-Clinical-Diagnostics-Announce-by-SCIEX) and Thermo Fisher introduced the Cascadion SM lab analyzer (https://www.labmedica.com/aacc-2017/ articles/294770271/worlds-first-fully-integrated-lc-ms-ms-clinical-analyzer-unveiled.html) in order to lower the barriers of many laboratories to adopt LC–MS. The hyphenation of chromatography and mass spectrometry has its primary values in relatively fast detection and analysis of multiple analytes in a single sample with high sensitivity and high selectivity - the key challenge and requirement to detect and quantify low-concentration analytes. Currently, the most widely used separation columns for the HPLC–MS in a clinical laboratory have an inner

5000 publications from January 1st, 2020 – February 1st, 2021.

**4**

The use of MS technology for measurement and analysis of clinically important peptides and protein biomarkers will definitively increase with further improving MS technology. It is clear that personalized medicine will become the major field of further development of targeted therapy and MS will be one of the major players in identifying both therapeutically targets and therapeutical agents. It is with great certainty that MS applications for evaluation of protein and peptide-based, or even the mRNA-based therapeutics, will play a crucial part for the quality control of the therapeutics, evaluating drug efficacy, or investigating therapeutic response.

Another issue is the miniaturization of MS and LC–MS systems that can be used portable systems or be applied in smaller field-laboratories. Certain advances were already achieved on developing such devises [16–23] that are being used in a number of analyses.

To conclude, mass spectrometry is a powerful analytical technology that still has not developed her full potential for use in clinical laboratory although its' use is growing. Different mass spectrometry-based devices have been approved for screening newborns, identifying microbes and fungus in cultures of human cells or for detecting measuring the concentrations of drugs (therapeutic and illicit) in body fluids. The development of large and integrated HPLC–MS systems for detecting and measuring peptides or proteins in clinical laboratories is still waiting to happen but mass spectrometry has already gained access to all areas of medical research and diagnostics.

*Mass Spectrometry in Life Sciences and Clinical Laboratory*
