Relative Quantification of Lipid Isomers in Imaging Mass Spectrometry Using Gas-Phase Charge Inversion Ion/Ion Reactions and Infrared Multiphoton Dissociation

• Published in: Analytical chemistry (Washington) Vol. 95; no. 48; pp. 17766 - 17775
• Main Authors: Bonney, Julia R, Kang, Woo-Young, Specker, Jonathan T, Liang, Zhongling, Scoggins, 4th, Troy R, Prentice, Boone M
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 05.12.2023
• Subjects: Animals; Anions; Brain; Carbon; Composition; Dissociation; Fragmentation; Infrared lasers; Inversion; Ion charge; Ionization; Isomers; Lecithin; Lipids; Mass spectrometry; Mass spectroscopy; Medical imaging; Neuroimaging; Phosphatidylcholine; Phosphatidylcholines - chemistry; Rats; Reaction products; Reagents; Scientific imaging; Spatial distribution; Spectrometry, Mass, Electrospray Ionization - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tissues; Workflow
• ISSN: 0003-2700; 1520-6882; 1520-6882
• DOI: 10.1021/acs.analchem.3c03804

Accurate structural identification of lipids in imaging mass spectrometry is critical to properly contextualizing spatial distributions with tissue biochemistry. Gas-phase charge inversion ion/ion reactions alter the ion type prior to dissociation to allow for more structurally informative fragmentation and improve lipid identification at the isomeric level. In this work, infrared multiphoton dissociation (IRMPD) was interfaced with a commercial hybrid Qh-FT-ICR mass spectrometer to enable the rapid fragmentation of gas-phase charge inversion ion/ion reaction products at every pixel in imaging mass spectrometry experiments. An ion/ion reaction between phosphatidylcholine (PC) monocations generated from rat brain tissue via matrix-assisted laser desorption/ionization (MALDI) and 1,4-phenylenediproprionic acid reagent dianions generated via electrospray ionization (ESI) followed by IRMPD of the resulting product ion complex produces selective fatty acyl chain cleavages indicative of fatty acyl carbon compositions in the lipid. Ion/ion reaction images using this workflow allow for mapping of the relative spatial distribution of multiple PC isomers under a single sum composition lipid identification. Lipid isomers display significantly different relative spatial distributions within rat brain tissue, highlighting the importance of resolving isomers in imaging mass spectrometry experiments.