이민규 (한국과학기술연구원)

이재익 (한국과학기술연구원)

이민규 (한국과학기술연구원)

김민주 (한국과학기술연구원)

강민식 (한국과학기술연구원)

이지현 (한국과학기술연구원)

오한빈 (서강대학교)

차상원 (동국대학교)

이재익 (한국과학기술연구원)

  Carboxylic acid-containing metabolites are essential metabolic intermediates in pathways such as the TCA cycle and serve as key indicators of acidity, microbial metabolism, authenticity and lipid origin in food science. Despite their broad importance, direct LC–MS analysis of carboxylic acids remains challenging because their high polarity and anionic character result in weak chromatographic retention and unstable signal responses. Furthermore, electron-rich carboxylate moieties readily interact with metal surfaces along the LC–MS flow path, leading to peak tailing, signal suppression, or even complete signal loss.

To overcome these limitations, a simple and effective (O)-silylation derivatization method was developed to enhance electrospray ionization efficiency and improve chromatographic behavior. The derivatization increased the hydrophobicity of the analytes and masked metal-coordination sites of the carboxyl groups. These effects increased chromatographic retention and produced sharper, more symmetric peaks. Derivatization also shifted the ionization detection mode from negative to positive ESI, thereby increasing signal intensity. These improvements enabled the reliable LC–MS analysis of small, polar, and metal-sensitive carboxylic acids with enhanced analytical sensitivity and reproducibility. This (O)-silylation strategy offers a practical approach for the LC–MS analysis of carboxylic acids and is expected to be applicable across diverse research fields.

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. RS-2023-NR076398).