Fishing for lipid lactones using selective reaction and characteristic fragmentation pattern

Area of Science:

• Lipidomics
• Analytical Chemistry
• Biochemistry

Background:

• Lipid mediators (LMs) are crucial signaling molecules, but identifying all LM classes remains challenging.
• Lactone-containing lipids, potentially important LMs, are often overlooked due to low ionizability and instability.
• Existing lipidomic methods do not routinely target these lactone lipids, limiting their discovery.

Purpose of the Study:

• To develop a selective method for identifying lipid lactones in complex biological matrices.
• To overcome the limitations of current lipidomic approaches in detecting lactone-containing lipids.

Main Methods:

• A novel method involving selective reaction of lactones with 1-(3-aminopropyl)imidazole.
• Cation exchange solid-phase extraction for sample cleanup.
• Liquid chromatography-tandem mass spectrometry (LC/MS/MS) for identification and characteristic fragmentation pattern analysis.

Main Results:

• Successful detection of saturated and unsaturated aliphatic ɣ and δ lactone model compounds in human serum.
• Identification of unique MS/MS fragmentation patterns specific to the reaction products of lactones.
• Demonstrated selectivity, as reaction products from esters and free fatty acids did not match the characteristic lactone fragmentation.

Conclusions:

• The developed method enables highly selective detection of lipid lactones within complex biological samples.
• This approach can overcome previous analytical challenges associated with lactone lipid identification.
• The method complements existing lipidomic strategies, facilitating the discovery of new lipid mediators.