Chemical derivatization strategy for mass spectrometry‐based lipidomics

Abstract

Lipids, serving as the structural components of cellular membranes, energy storage, and signaling molecules, play the essential and multiple roles in biological functions of mammals. Mass spectrometry (MS) is widely accepted as the first choice for lipid analysis, offering good performance in sensitivity, accuracy, and structural characterization. However, the untargeted qualitative profiling and absolute quantitation of lipids are still challenged by great structural diversity and high structural similarity. In recent decade, chemical derivatization mainly targeting carboxyl group and carbon-carbon double bond of lipids have been developed for lipidomic analysis with diverse advantages: (i) offering more characteristic structural information; (ii) improving the analytical performance, including chromatographic separation and MS sensitivity; (iii) providing one-toone chemical isotope labeling internal standards based on the isotope derivatization regent in quantitative analysis. Moreover, the chemical derivatization strategy has shown great potential in combination with ion mobility mass spectrometry and ambient mass spectrometry. Herein, we summarized the current states and advances in chemical derivatization-assisted MS techniques for lipidomic analysis, and their strengths and challenges are also given. In summary, the chemical derivatization-based lipidomic approach has become a promising and reliable technique for the analysis of lipidome in complex biological samples.

Metabolomics and its Applications in Cancer Cachexia

“…It can be qualitatively and quantitatively employed to analyze various sample sources, which include cells or tissues extract, bio-fluids, and microorganisms caused by genetically engineered or drug treatment. Metabolomic analyses usually focus on small molecular metabolites such as amino acids, lipids, small molecular peptides, and organic acids with a relative molecular weight of less than 1,000 Da (Nicholson et al, 1999;Fiehn et al, 2000;Xia and Wan, 2021). Generally, metabolomics includes two tools: non-targeted and targeted metabolomics.…”

Review of Recent Advances in Lipid Analysis of Biological Samples via Ambient Ionization Mass Spectrometry

“…Although the appealing advantages of AIMS promote the spatial visualization of unsaturated lipid isomers within various biological tissue samples, the low sensitivity of AIMS caused by a low ionization and transmission efficiency remains the main drawback that hinders the widespread application of AIMS in lipid imaging. In this regard, more and more effective chemical derivatization approaches will need to be developed [88].…”

Aziridination-assisted mass spectrometry of nonpolar lipids with isomeric resolution

“…Mass spectrometry (MS) has emerged as a powerful tool for lipidomic studies that measure special and temporal alterations in the composition of lipids due to its high specificity and sensitivity. Recent efforts in MS-based lipid analysis-including ion activation methods 4 , chemical derivatization, 5,6 and ion mobility spectrometry 7 -focus on identification of lipid isomers with the same molecular formulas but different structures and functions. Polar lipids, such as glycerophospholipids, often dominate the mass spectrum, as they can be pre-charged or are more effectively ionized in electrospray.…”

“…However, nonpolar lipids, which account for over a third of the total lipids in human epidermal cells, 8 cannot be ionized well, thus their species and isomeric forms are more challenging to be detected by MS. Current methods for improving ionization efficiencies of nonpolar lipids include radical cation formation by ultraviolet photodissociation (UVPD) which requires specific instrumentation. 4,6 Another approach is derivatization through reactions with specific functional groups such as carboxyl 6 or hydroxy 5 groups. While these derivatizations are effective, they are limited in their application, as many important nonpolar lipids do not contain these groups.…”