The basics of mass spectrometry in the twenty-first century

Key Points Mass spectrometry has become an indispensable analytical tool in all types of drug discovery applications. Development of two ionization techniques, electrospray (ESI) and matrix assisted laser desorption/ionization (MALDI), has revolutionized the applicability of mass spectrometry to almost any biological molecule. Many types of mass analyzers can be used in drug discovery applications, but the majority of the work is done with quadrupoles, quadrupole ion traps, and time-of-flight mass spectrometers. Fourier-transform ion-cyclotron resonance (FT-ICR) mass spectrometry is playing an increasingly important role as a mass analyzer. Tandem mass spectrometry (MS/MS) is a crucial technique in many applications related to drug discovery. MS/MS involves multiple stages of mass analysis. Quadrupole ion traps and FT-ICR mass spectrometers perform MS/MS by separating the stages in time. Other combinations of analyzers such as quadrupole/time-of-flight and multiple quadrupole mass spectrometers perform MS/MS using sequential analyzers. Enormous advances in our understanding of the chemistry underlying life processes have identified new targets for therapeutic agents. The discovery of effective therapeutics to address these targets is often accomplished through parallel synthetic and screening efforts. In almost all cases, what has enabled target identification and allowed parallel approaches to drug discovery to be effective are the development of either new analytical tools or the improvement of currently existing ones. Among these tools, mass spectrometry has evolved to become an irreplaceable technique in the analysis of biologically related molecules. This article will guide researchers in drug discovery through the basic principles of mass spectrometry.