The composition and structure of protein corona represents a crucial factor that controls the biological properties and fate of nanomaterials. While the composition of the corona can relatively easily be investigated by conventional bottom-up proteomics, assessing the spatial orientation of a protein in the corona (i.e assessing which epitopes are exposed on the outer surface) is still a challenging and time-consuming task. In this paper, we show that labeling the corona proteins with isobaric tags in their native conditions, and the subsequent analysis of MS/MS spectra of tryptic peptides, allows an easy and high-troughput assessment of the inner/outer orientation of the corresponding proteins in the original corona.