One caveat of classical HDX-MS workflows is the need to keep LC separations short and under quench conditions (pH 2.5 and 0-1C) to minimise deuterium/hydrogen back-exchange . This, in turn, limits available LC-MS peak capacity, which can often result in insufficient detection and identification of peptides derived from the protein(s) of interest, thereby leading to low sequence coverage and redundancy. This is particularly problematic for challenging targets such as G protein-coupled receptors (GPCRs) and other integral membrane proteins (IMPs), which often require lengthy screening and optimisation of HDX-MS conditions to obtain high-quality results . In an attempt to alleviate this issue, HDX-MS practitioners have previously adopted ion mobility (IM) ; an analytical technique which separates gas-phase ions based on their mobilities in an inert buffer gas under the influence of an electric field . IM can operate on the millisecond timescale. Thus, its use in bottom-up LC-MS instrumentation can provide an additional orthogonal dimension of peptide separation without increasing the length of the LC-MS experiment.