Aziridination-Enabled Structural and Quantitative Lipidomics

Chemical derivatization has long been employed to enhance the structural characterization of lipids by mass spectrometry (MS). In recent years, olefin aziridination has emerged as a powerful and versatile strategy in lipidomics, driven by its ability to selectively target carbon-carbon double bonds (C═C bonds) and to introduce nitrogen-containing functionalities that facilitate both structural elucidation and quantitative analysis. Aziridination-enabled MS approaches provide reliable C═C bond localization through diagnostic fragmentation, while simultaneously improving ionization efficiency, particularly for nonpolar lipid classes. A diverse range of aziridination chemistry has been developed, each offering distinct advantages for lipid analysis. In this review, we summarize recent advances in aziridination-enabled MS methodologies, with an emphasis on reaction development and analytical performance. We further highlight applications across biological and complex sample systems. These developments highlight aziridination-assisted MS as a powerful strategy for precision lipidomics with isomer-resolved capability and accurate quantification.