The ZrO 2 beads and cartridge are then disposed after each experiment. Other approaches for phospholipid removal that avoid the use of ZrO 2 beads have also been developed, including TCA precipitation and the use of size-exclusion chromatography (SEC) . Here, we report an alternative chromatographic approach which enables online, regeneratable phospholipid trapping by a ZrO 2 bead column. This exploits the Lewis acid chemistry of ZrO 2 -whilst avoiding the need for precipitation, size separation, filtration or bead disposal -to offer a robust automated system for HDX, digestion and LC-MS analysis of proteins within lipid environments.