Hydrogen/deuterium exchange-mass spectrometry (HDX-MS) has become a well-established methodology for probing protein higher-order structure in solution . To achieve this, HDX-MS measures the time-dependent exchange of amide hydrogens of the polypeptide backbone with deuterium in the surrounding solvent; a reaction termed HDX. The HDX rate in folded proteins is primarily dependent on hydrogen bonding status Consequently, changes in HDX-MS readout can report on a variety of protein behavioural characteristics such as conformational dynamics , folding pathways [6], protein-protein and protein-small molecule interactions , as well as epitope mapping for biopharmaceutical characterisation . In a typical HDX-MS experiment, proteins are first incubated in deuterated buffer to induce spontaneous deuterium incorporation into the polypeptide backbone, followed by reaction quenching by dropping solution pH and temperature to 2.5 and 0-1C, respectively.