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The basics of mass spectrometry in the twenty-first century

Nature Reviews Drug Discovery volume 2, pages 140–150 (2003)Cite this article

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.

Abstract

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.

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Figure 1: Basic components of a typical mass spectrometer used in drug discovery.
Figure 2: A comparison of the mass spectra for cytochrome c generated using electrospray ionization and matrix-assisted laser desorption/ionization.
Figure 3: Pictorial diagrams of the common beam mass analysers viewed from above.
Figure 4: Pictorial diagrams of the common trapping mass analysers.
Figure 5: Schematic diagram of tandem mass spectrometry.

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Authors and Affiliations

  1. Department of Chemistry, University of North Carolina, Chapel Hill, 3290, North Carolina, USA

    Gary L. Glish

  2. Department of Chemistry, University of Massachusetts, 710 North Pleasant Street, Amherst, 9336, Massachusetts, USA

    Richard W. Vachet

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  1. Gary L. Glish
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Correspondence to Gary L. Glish.

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FURTHER INFORMATION

International Mass Spectrometry Society

American Society for Mass Spectrometry

Enclyclopedia of Life Sciences

Mass spectrometry in biology

Glossary

ANALYTE

The substance being analyzed.

PROTONATION

The addition of one or more protons to a compound so that the net charge of the compound is positive.

DEPROTONATION

The removal of one or more protons from a compound so that the net charge of the compound is negative.

KINETIC ENERGY

The energy associated with a substance because of its translational motion; equal to one-half its mass times the square of its velocity.

INTERNAL ENERGY

The energy associated with the movement of the atoms and electrons in a chemical compound relative to one another; the increase in the internal energy of a compound leads to an increase in its temperature and in some cases dissociation.

STOICHIOMETRY

The quantitative relationship between the reactants and products in a chemical reaction.

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Glish, G., Vachet, R. The basics of mass spectrometry in the twenty-first century. Nat Rev Drug Discov 2, 140–150 (2003). https://doi.org/10.1038/nrd1011

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