Small changes in structure can lead to loss of activity and/or an increase in aggregation. Structure-activity relationships are not isolated to the epitope either – both proximal and distal changes can have deleterious impacts on a biologics’ function. Hydrogen-deuterium exchange mass spectrometry (HDX-MS) enables investigation of these localized or global changes through the exchange of labile protons with deuterium ions. The rate and magnitude of the exchange provides information regarding protein dynamics, conformation and interactions. This talk will focus on the increased resolution of HDX-MS via hardware improvements and how ion mobility spectroscopy aides in deconvolution and simplifies complex spectra.