To evaluate Cyclic IMS performance in the HDX-MS context, non-deuterated peptide mapping was performed and benchmarked relative to previous generation SYNAPT G2-Si instrumentation with linear TWIM technology (Figure ). To maximise comparability between results, identical batches of purified protein and buffers were used, as well as identical UPLC equipment including analytical, trapping and digestion columns. Therefore, the only variation between comparative experiments was the mass spectrometer used and their tuning parameters (which were chosen based on manufacturer recommendations).