Electrospray Ionization Mass Spectrometry as a Valuable Tool in the Characterization of Novel Primaquine Peptidomimetic Derivatives

Abstract

Novel primaquine-derived antimalarials have been extensively characterized by electrospray ionization-ion trap mass spectrometry (ESI-MS). Experiments by in-source collision-induced dissociation (CID) in the nozzle–skimmer region (NSR) or by tandem mass spectrometry (MS/MS) are shown to be most valuable tools for the physico–chemical characterization of these 8-aminoquinolinic drugs that also bear the biologically relevant imidazolidin-4-one scaffold. It was possible to find parallelism between compound stability in the NSR and its reactivity towards hydrolysis at physiological pH and T. Moreover, MS/MS fragmentation patterns were characteristic for each family, providing a means for structural distinction of isomers and allowing interesting correlations to be found between the relative abundance of particular fragments and relevant structure–activity determinants, such as the Charton steric parameter, ν. In conclusion, this work provides a solid ground for establishing ESI-MS as a key tool for the physico–chemical characterization of biopharmaceuticals bearing the 8-aminoquinoline and/or the imidazolidin-4-one moieties.