Derivatization of carboxyl groups improves the detection sensitivity of fatty acids in mass spectrometry.

Derivatization targeting C=C bonds allows for the analysis of fatty acid positional isomers.

Comprehensive fatty acid characterization enables both high sensitivity and precise double bond localization.

Fatty acids (FAs) play a vital role in various physiological processes in the human body, and the analysis of FA isomers is of utmost importance in the research of various diseases and FA metabolic pathways. Over the last few years, the use of chemical derivatization methods to alter the composition of FAs has been found to be highly effective in overcoming the drawback of poor sensitivity in mass spectrometry (MS) analysis due to the poor ionizability of functional groups in FA molecules. Furthermore, certain chemical derivatization methods have enabled detection of C=C and differentiation of cis-trans isomers. As a result, the development and use of chemical derivatization-based MS to analyze FAs has gained significant interest. This review highlights technological innovations in the development of MS detection methods for unsaturated FAs (UFAs) based on chemical derivatization. Special emphasis is placed on two significant strategies: carboxyl group derivatization and C=C derivatization. In addition, it focuses on applications in various fields, discusses persistent challenges, and explores potential future directions. This review aims to provide a perspective on the advanced design and development of MS detection methods of FAs based on chemical derivatization.

Fatty acids

Chemical derivatization

Unsaturated C=C bonds

Carboxyl group

Mass spectrometry

© 2025 The Authors. Published by Elsevier B.V. on behalf of Xi’an Jiaotong University.