Stable-Isotope N‑Me Aziridination Enables Accurate Quantitative CC Isomeric Lipidomics

Accurate lipid quantification is
essential to revealing their roles
in physiological and pathological processes. However, difficulties
in the structural resolution of lipid isomers hinder their further
accurate quantification. To address this challenge, we developed a
novel stable-isotope N-Me aziridination strategy that enables simultaneous
qualification and quantification of unsaturated lipid isomers. The
one-step introduction of the 1-methylaziridine structure not only
serves as an activating group for the CC bond to facilitate
positional identification but also as an isotopic inserter to achieve
accurate relative quantification. The high performance of this reaction
for the identification of unsaturated lipids was verified by large-scale
resolution of the CC positions of 468 lipids in serum. More
importantly, by using this bifunctional duplex labeling method, various
unsaturated lipids such as fatty acids, phospholipids, glycerides,
and cholesterol ester were accurately and individually quantified
at the CC bond isomeric level during the mouse brain ischemia.
This study provides a new approach to quantitative structural lipidomics.