A full understanding and mediation of nanoparticle-serum protein interactions is key to design nanoparticles with vivid functions within the body, and to solve this problem one needs to differentiate and characterize individual nano-protein conjugates. In this paper, the authors applied capillary electrophoresis combined with inductively coupled plasma mass spectrometry detection to study the behavior of gold nanoparticles of different geometry, size and surface functionalization upon interacting with serum proteins and their mixtures. Due to high-resolution and -sensitivity benefits of this combined technique baseline separations were attained for free nanoparticles (at real-life doses) and different protein conjugates, and the conversion into the protein-bound form was scrutinized in terms of reaction time.