Acid-base-driven matrix-assisted mass spectrometry for targeted metabolomics

Area of Science:

• Analytical Chemistry
• Biochemistry
• Mass Spectrometry

Background:

• Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry is vital for analyzing large biomolecules.
• Conventional matrix selection is empirical and creates interfering ions, limiting its use in metabolomics.

Purpose of the Study:

• To introduce MAILD, a rational protocol for matrix selection in MALDI-MS.
• To demonstrate MAILD's applicability to small molecule analysis, including metabolomics and clinical diagnostics.

Main Methods:

• Developed a matrix selection protocol based on Brønsted-Lowry acid-base theory.
• Applied the MAILD protocol to analyze metabolites in various biological samples.

Main Results:

• Successfully detected numerous metabolites from key metabolic pathways (e.g., Krebs' cycle, fatty acid biosynthesis).
• Demonstrated MAILD's effectiveness in analyzing extracts, biofluids, and tissues from diverse organisms.
• Showcased applications in metabolomics, biological screening, profiling, imaging, and clinical diagnostics.

Conclusions:

• MAILD shifts matrix selection from empirical to rational design.
• This approach significantly advances small molecule analysis using MALDI-MS, overcoming limitations of conventional methods.