The field of lipidomics, as coined in 2003, has made profound advances and been rapidly expanded. The mass spectrometry-based strategies of this analytical methodology-oriented research discipline for lipid analysis are largely fallen into three categories: direct infusion-based shotgun lipidomics, liquid chromatography-mass spectrometry-based platforms, and matrix-assisted laser desorption/ionization mass spectrometry-based approaches (particularly in imagining lipid distribution in tissues or cells). This review focuses on shotgun lipidomics. After briefly introducing its fundamentals, the major materials of this article cover its recent advances. These include the novel methods of lipid extraction, novel shotgun lipidomics strategies for identification and quantification of previously hardly accessible lipid classes and molecular species including isomers, and novel tools for processing and interpretation of lipidomics data. Representative applications of advanced shotgun lipidomics for biological and biomedical research are also presented in this review. We believe that with these novel advances in shotgun lipidomics, this approach for lipid analysis should become more comprehensive and high throughput, thereby greatly accelerating the lipidomics field to substantiate the aberrant lipid metabolism, signaling, trafficking, and homeostasis under pathological conditions and their underpinning biochemical mechanisms.
Charge-remote fragmentation has been well recognized as an effective approach for dissociation of long aliphatic chains. Herein, we exploited this approach for structural identification of all fatty acids including saturated, unsaturated, and modified ones by using electrospray ionization tandem mass spectrometry (ESI-MS/MS) after one-step derivatization of a charge-carried reagent through an amidation reaction. We tested the approach with different charge-carried reagents with respective to the hydrophobicity, charge strength, and distance from the charge to the carboxyl group. We found all the derivatives with these reagents could yield informative charge-remote fragmentation patterns regardless of the different chemical and physical properties of the reagents and these informative fragmentation patterns all could be effectively used for structural elucidation of lipid species containing a carboxyl group. We further found that the distinguished charge-remote fragmentations of fatty acid isomers enabled us to determine the composition of these isomers without any chromatographic separation. Finally, the abundant fragments yielded from individual derivatized moiety enabled us to sensitively quantify the individual species containing a carboxyl group. The described approach was a great extension to the multidimensional mass spectrometry-based shotgun lipidomics for global analysis of fatty acids including isomers and modifications. We believe that this approach could greatly facilitate the identification of the biochemical mechanisms underlying numerous pathological conditions.
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