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-MS are shown to be most valuable tools for the physicochemical 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, tandem-MS fragmentation patterns were characteristic for each family, providing a means for structural distinction of isomers and allowing to find interesting correlations between the relative abundance of particular fragments and relevant structure-activity determinants, such as Charton steric parameter, v. In conclusion, this work provides solid grounds to establish ESI-MS as a key tool for the physicochemical characterization of biopharmaceuticals bearing the 8-aminoquinoline and/or the imidazolidin-4-one moieties.