Preface

Mass spectrometry (MS) is one of the most used analytical tools for analyzing complex organic and inorganic samples. Analyses of biological samples in life sciences, medical sciences, clinical laboratories, food processing, research, and quality control in the pharmaceutical industry are routinely performed using different MS approaches. Furthermore, MS is applied for controlling the origin of food and identifying mislabeled products and toxins in foods [1–4]. Identification of illicit substances and drugs of abuse relies heavily on MS, and its use is widely reported [5–11]. Technological innovations, such as improved ion transfer, improved ionization efficiency, and mass resolution of mass spectrometers, have significantly improved the data generated and widened the field of use.

A significant number of analytical methods for MS in clinical laboratories have been developed in the recent past. Development of these methods has rapidly increased as the COVID-19 pandemic holds humankind in its grip, and techniques for fast high-performance liquid chromatography-mass spectrometry (HPLC-MS) have been developed and applied.

In the chapter "Mass Spectrometry in Clinical Laboratories," Miletić Vukajlović and Panić-Janković discuss the development of MS methods for newborn screening and detection of modifications in the metabolome of amino acids that can lead to severe health conditions. Identifying such changes has helped develop more effective treatment methods. The authors further discuss the detection and analysis of antibiotics in clinical samples, which is an important topic considering the growing resistance of bacteria against the antibiotics currently in use.

In the chapter "Identification of Peptides and Proteins in Illegally Distributed Products by MALDI-TOF-MS," Amini et al. address and discuss using MAlDI MS to trace illegal products. The market for illegal medical products, pharmaceuticals, and food is an ever-growing one, and counterfeit products are a severe threat to human health. Proteins and peptides can be identified and characterized quickly by applying MALDI, and illicit products can be traced and eliminated from the market.

Research and analysis of stem cells has given hope to many regarding the treatment of rare diseases and significant health conditions. Vaňhara et al. discuss the mass spectrometry methods for analyzing and characterizing the single intact embryonic stem cell before being used for a patient's treatment In the chapter "Intact Cell Mass Spectrometry for Embryonic Stem Cell Biotyping," Vaňhara et al. discuss MS methods for analyzing and characterizing a single, intact embryonic stem cell before using it to treat patients. MALDI-TOF MS, based on the principle of mass spectrometric "biotyping" of bacteria, is currently being used to analyze single cells. Mass spectra generated by MALDI contain information that helps to reveal the cell's immunophenotype and activation state. Results from MS allow for the identification of changes and posttranslational modifications associated with the molecular phenotype of the applied cell lines.

**II**

**Chapter 7 121**

Intact Cell Mass Spectrometry for Embryonic Stem Cell Biotyping *by Petr Vaňhara, Lukáš Moráň, Lukáš Pečinka, Volodymyr Porokh, Tiziana Pivetta, Sebastiano Masuri, Eladia Maria Peña-Méndez,* 

*José Elías Conde González, Aleš Hampl and Josef Havel*

König et al. describes HPLC hyphenated to M.S. for Identification of Protoporphyrin IX (PPIX) that can serve as a potential biomarker for cancer screening in neurological cancer, especially the neuroblastoma In the chapter "Protoporphyrin IX Analysis from Blood and Serum in the Context of Neurosurgery of Glioblastoma" König et al. describe HPLC for identifying protoporphyrin IX (PPIX), which is a potential biomarker for cancer screening in neurological cancer, especially neuroblastoma. The benefit of using MS to analyze a complex biological sample is shown in its ability to detect different forms of metal-conjugated PPIX based on fragmentation mass spectra. The methods described also show that MS has a significant advantage over the traditionally used fluorescence-based methods.

One of the fields with the most dynamic growth in the clinical application of MS is mass spectrometry imaging (MSI). The improvement of laser technology with better and more sensitive detectors has shown the enormous potential of this technology. MSI in the clinical field is still overwhelmingly used for digital pathology, particularly for brain imaging. In the chapter "Mass Spectrometry Imaging of Neurotransmitters," Stumpo describes the use of MSI for imaging neurotransmitters, which have broad and significant implications due to their involvement in the complex biological processes that occur in the brain.

The most advanced analytical instrumentation cannot fix the mistakes made during sample preparation for HPLC-MS analysis. Dapić et al. address this critical topic In the chapter "Trends in Sample Preparation for Proteome Analysis," Dapić et al. addresses this critical topic. Depending on the analysis to be performed, different types of sample preparation are utilized. This step is the key to successful research in proteomics. However, there is still no consensus in the proteomics and clinical community on how to treat the biological sample and which set-up should be used to prepare proteins from clinical samples. This chapter focuses on sample preparation for bottom-up proteome profiling using MS and, especially, for preparing tissue samples from fresh frozen and formalin-fixed paraffin-embedded material.

MS is a powerful analytical technique that still has not developed its full potential for use in clinical laboratories, although its use is growing. Different MS-based devices have been approved for screening newborns, identifying microbes and fungus in cultures of human cells, and detecting and 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 yet to happen. However, MS has already gained access to all areas of medical research and diagnostics.

> **Goran Mitulović** Medical University of Vienna, Austria

> > **V**

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