Chiral α-Hydroxy Acid Discrimination in Tumor Tissues and Food Samples via Derivatization-Assisted MALDI-TIMS-MS

Area of Science:

• Analytical Chemistry
• Metabolomics
• Biochemistry

Background:

• Chiral metabolite analysis is vital for understanding metabolic disorders and disease biomarkers.
• Accurate enantiomeric ratio determination is essential for clinical diagnostics and food safety.

Purpose of the Study:

• To develop and optimize a method for chiral discrimination of α-hydroxy acids, specifically 2-hydroxyglutarate (2-HG) and lactic acid (LA).
• To enable precise determination of enantiomeric ratios in complex biological and food matrices.

Main Methods:

• Integration of a chiral derivatization strategy with matrix-assisted laser desorption/ionization (MALDI) and trapped ion mobility spectrometry (TIMS).
• Optimization of derivatization reagents (TSPC and DATAN) and alkali metal ion adducts for diastereomeric conversion.
• High-resolution enantiomer separation and quantification.

Main Results:

• Successful chiral separation of 2-HG and LA enantiomers with high resolution.
• Demonstrated ability to determine enantiomeric ratios as low as 5.8%.
• Sensitive identification of 2-HG in IDH-mutated tumor tissues and precise determination of LA enantiomers in fermented foods.

Conclusions:

• The developed method offers a powerful tool for chiral metabolite analysis in complex samples.
• This approach has significant potential for advancing biomarker screening, food safety, pharmaceutical development, and clinical diagnostics.