Mass spectrometry as test bench for medicinal chemistry studies

This review describes how mass spectrometry can be used as a powerful test bench to obtain information on the biological activity of target compounds. Considering that mass spectrometry is based on the chemical reactivity of the analytes, it is possible to investigate the stability of the active compounds, to predict their behaviour in the environment of interest, and to obtain structure–reactivity relationships for new molecules of pharmacological interest. Electron ionization and metastable ion studies give evidence of the correlation between the mutagenic properties of a series of aryl and heteroaryl triazenes and mass spectrometric data. A linear relationship between the energetics of C(O)–O bond cleavage of some carbamic acid O-aryl esters and their FAAH inhibition activity has been proved by electrospray-ionization ion-trap mass spectrometry. An inverse correlation between the stability and cytotoxic activity of some copper complexes has been clearly established by electrospray-ionization mass spectrometry. Moreover, because of the sensitivity and specificity of mass spectrometry, it has been possible to determine and characterize impurities that in some cases can be the real bioactive compound.