Electrospray ionization mass spectrometry as a valuable tool in the characterization of novel primaquine peptidomimetic derivatives

Abstract

Novel primaquine-derived antimatarial!, 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 midazolidin-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, nu. In conclusion, this work provides a solid ground for establishing ESI-MS as a key toot for the physico-chemical characterization of biopharmaceuticals bearing the 8-aminoqunoline and/or the imidazolidin-4-one moieties.. - Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) [PTDC/QUI/65142/2006]; FCT [SFRH/BPD/48345/2008]. - Thanks are due to Fundacao para a Ciencia e a Tecnologia (FCT, Portugal) for financial support through Project PTDC/QUI/65142/2006. NV thanks FCT for Post-Doctoral fellowship SFRH/BPD/48345/2008. PG and RM thank FCT for support through pluriannual funding to CIQUP and SUPi/SUPMed.UL, respectively.