Analysis of lipids using 2,4,6-trihydroxyacetophenone as a matrix for MALDI mass spectrometry

Area of Science:

• Analytical Chemistry
• Biochemistry
• Mass Spectrometry

Background:

• Lipid analysis presents significant challenges due to diverse chemical properties.
• Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a key technique for lipid identification.
• Novel MALDI tandem time-of-flight (TOF/TOF) instrumentation enhances structural elucidation capabilities.

Purpose of the Study:

• To evaluate 2,4,6-trihydroxyacetophenone (THAP) as a matrix for comprehensive lipid analysis.
• To establish a sample preparation method for enhanced lipidomics studies.
• To assess the utility of THAP-MALDI-MS/MS for structural characterization of various lipid classes.

Main Methods:

• Utilized matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) with 2,4,6-trihydroxyacetophenone (THAP) as the matrix.
• Analyzed diverse lipid classes: neutral storage lipids (triacylglycerols), polar membrane lipids (glycerophospholipids, sphingolipids), and glycosphingolipids.
• Developed a sample preparation protocol involving selective alkali salt doping for MS/MS experiments.

Main Results:

• THAP demonstrated versatility as a matrix for routine lipidomics analysis of biological samples.
• Selective alkali salt doping (sodiated and lithiated molecules) significantly improved MS/MS experiments.
• This approach yielded both high sensitivity for peak detection and enhanced structural information, including acyl group identification.

Conclusions:

• 2,4,6-trihydroxyacetophenone (THAP) is an effective matrix for broad lipid class analysis via MALDI-MS.
• Alkali metal doping combined with MALDI-MS/MS provides a powerful strategy for sensitive and structurally informative lipidomics.
• The developed methodology enables simultaneous sensitive detection and reliable structural elucidation of lipids from complex biological matrices.