Aeer inves9ga9on of the chromatographic performance mass spectrometric interfacing was explored by coupling the separa9on system to a Thermo Scien9fic Q Exac9ve UHMR mass spectrometer with a mass range adequate for the analysis of macromolecules in the megadalton range. While previous inves9ga9ons clearly show that na9ve mass spectrometry does not facilitate mass determina9on of AAVs, literature also suggest that full and empty par9cles carry the same extent of posi9ve charges aeer ioniza9on . Consequently, their MS signals appear in different regions in the m/z domain, depending on whether they carry cargo DNA or not, allowing for their discrimina9on .