title: Trimethylation enhancement using diazomethane (TrEnDi) II: rapid in-solution concomitant quaternization of glycerophospholipid amino groups and methylation of phosphate groups via reaction with diazomethane significantly enhances sensitivity in mass spectrometry analyses via a fixed, permanent positive charge.
abstract: A novel mass spectrometry (MS)-based lipidomics strategy that exposes glycerophospholipids to an ethereal solution of diazomethane and acid, derivatizing them to contain a net fixed, permanent positive charge, is described. The sensitivity of modified lipids to MS detection is enhanced via improved ionization characteristics as well as consolidation of ion dissociation to form one or two strong, characteristic polar headgroup fragments. Our strategy has been optimized to enable a priori prediction of ion fragmentation patterns for four subclasses of modified glycerophospholipid species. Our method enables analyte ionization regardless of proton affinity, thereby decreasing ion suppression and permitting predictable precursor ion-based quantitation with improved sensitivity in comparison to MS-based methods that are currently used on unmodified lipid precursors.
authors.affiliation: Department of Chemistry and ‡Institute of Biochemistry, Carleton University , Ottawa, Ontario K1S 5B6, Canada.
authors.forename: Karl V
authors.initials: KV
authors.lastname: Wasslen
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Canez
authors.forename: Hyunmin
authors.initials: H
authors.lastname: Lee
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Manthorpe
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Smith
mesh_terms: D003978:Diazomethane / Q000737:chemistry*; D020404:Glycerophospholipids / Q000737:chemistry; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods*; D008745:Methylation; D010710:Phosphates / Q000737:chemistry*
chemical_list: D020404:Glycerophospholipids; D010710:Phosphates; D003978:Diazomethane