Mass Spectrometry-Based Methods in CNS Drug Discovery

Proteins constitute most biochemically active components in biological systems and many of the FDA-approved biomarkers and drug targets. Mass spectrometry-based proteomics is the most comprehensive technique used for the quantitative profiling of proteins and the understanding of their function, structure, and dynamics. Increasingly, mass spectrometry is also used for studying lipids and metabolites, contributing to the emerging fields of lipidomics and metabolomics. Mass spectrometry imaging is an exciting advancement in the field that enables the spatial mapping of biomolecules within tissues, offering unprecedented insights into their distribution and localization. The mass spectrometry field is, however, a challenging topic as it requires expertise in biochemistry, analytical chemistry, and computational biology, and novel techniques are increasingly emerging. We review the basics of mass spectrometry instrumentation and its current applications in CNS drug discovery. Significant improvements in mass spectrometry technology have been made in recent years, which resulted in better throughput, streamlining, and robustness of analyses. Furthermore, the advent of novel techniques, including single-cell analysis, chemoproteomics, and data-independent acquisition methods—together with big data and artificial intelligence analyses—now opens up exciting opportunities across the whole spectrum of CNS drug discovery and development stages. This chapter will delve into these advancements and explore their implications for driving innovative drug development and biomarker research.