Lipids mediate several biological processes and have been studied extensively for their role in conditions including cardiovascular disease, aging, and cancer. Mass spectrometry-based lipidomics has undergo a huge expansion during the last decade due to advances in fragmentation for more efficient MS/MS and introduction of more affordable high resolution accurate mass (HRAM) instrumentation. The most common analytical lipidomics approaches utilize LC-MS/MS on either triple quadrupole platforms (for targeted, quantitative studies) or high resolution instrumentation (for untargeted, discovery studies). Another emerging technique is ion mobility spectrometry (IMS), a gas-phase separation technique based on differences in size, shape, and charge of lipid ions. This has provided improved resolution for several types of structurally similar lipid isomers such as cis vs. trans double bond isomers. Despite the advances made in MS-based lipidomics, difficulties in accurate and complete characterization of the lipidome have prompted innovative, structure-specific approaches. Ozone-induced dissociation (OzID) has been established as a useful technique for selective cleavage of carbon-carbon double bonds, and this approach allows for comparison of precursor and fragment ions for determination of double bond location within a lipid. This presentation will highlight recent advances in solution-phase ozonolysis, in which a lipid extract (pre-ionization source) is exposed to 185 nm radiation from a mercury lamp, prompting carbon-carbon double bond cleavage. Studies are performed using an Agilent 6560 LC-IM-QTOF, allowing for acquisition of mobility and m/z data for both precursor and ozonolysis products. Lipid extracts from several tissue types (e.g., heart, liver, brain, etc.) are being analyzed to identify trends in different lipid classes common to each tissue. Additional fragmentation using collision induced dissociation (CID) following the drift tube is used to acquire information on the lipid head group. This approach is expected to significantly improve global identification of double-bond containing lipid isomers.

Ion mobility-mass spectrometry and ozone-Induced dissociation (OzID) methods for improved lipidomics analysis

2019 Spring National Meeting

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