Applications of mass spectrometry in early stages of target based drug discovery

Mass spectrometry (MS) has been applied to drug discovery for many years. With the advent of new ionization techniques, MS has emerged as an important analytical tool in identification and characterization of protein targets, structure elucidation of synthetic compounds, and early drug metabolism and pharmacokinetics studies. Two MS-based strategies, function-based and affinity-based, have been employed in recent years for screening and evaluation of compounds. In the function-based approach, the effects of compounds on the biological activity of a target molecule are measured. In the affinity-based approach, compounds are screened based on their binding affinities to target molecules. The interaction between targets and compounds can be directly evaluated by monitoring the formation of non-covalent target–ligand complexes (direct detection) or indirectly evaluated by detecting the compounds after separating bound compounds from unbound (indirect detection). Various techniques including high performance liquid chromatography (HPLC)–MS, size exclusion chromatography (SEC)–MS, frontal affinity chromatography (FAC)–MS and desorption/ionization on silicon (DIOS)–MS can be applied. The recent advances, relative advantages, and limitations of each MS-based method as a tool in compound screening and compound evaluation in the early stages of drug discovery are discussed in this review.