Metal Polycation Adduction to Lipids Enables Superior Ion Mobility Separations with Ultrafast Ozone-Induced Dissociation.

Specific lipid isomers are functionally critical, but their structural rigidity and usually minute geometry differences make separating them harder than other biomolecules. Such separations by ion mobility spectrometry (IMS) were recently enabled by new high-definition methods using dynamic electric fields, but major resolution gains are needed. Another problem of identifying many isomers with no unique fragments in ergodic collision-induced dissociation (CID) was partly addressed by the direct ozone-induced dissociation (OzID) that localizes the double bonds, but a low reaction efficiency has limited the sensitivity, dynamic range, throughput, and compatibility with other tools. Typically lipids are analyzed by MS as singly charged protonated, deprotonated, or ammoniated ions. Here, we explore the differential IMS (FAIMS) separations with OzID for exemplary lipids cationized by polyvalent metals. These multiply charged adducts have much greater FAIMS compensation voltages (