Biochemical applications of mass spectrometry in pharmaceutical drug discovery

Mass Spectrometry Reviews
Kieran F Geoghegan, Michele A Kelly

Abstract

Biochemical applications of mass spectrometry (MS) are important in the pharmaceutical industry. They comprise compositional analyses of biomolecules, especially proteins, and methods that measure molecular functions such as ligand binding. In early drug discovery, MS is used to characterize essential reagents and in structural biology. A number of MS-based methods have been proposed for use in high-throughput screening (HTS), but are unlikely to supplant established radiometric and fluorometric methods for this purpose. These methods, which include pulsed-ultrafiltration MS, frontal affinity chromatography-MS, and size-exclusion chromatography-MS, may ultimately be most successful in the post-screening lead development phase. In full development, MS is used heavily in the search for biomarkers that can be used to gauge disease progression and drug action. This review gives equal attention to the technical aspects of MS-based methods and to selective pressures present in the industrial environment that influence their chances of gaining wide application.

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