Methanol-driven esterification of volatile short-chain fatty acids in thermal desorption-based analysis
File(s)
Published version
Author(s)
Leung, Philip Kwan Hung
Wong, Alson Hubert Kwongyiu
Ma, Yiling
Yoo, Jungmin Jen
Bajo-Fernández, María
Type
Journal Article
Abstract
Breath volatile organic compound analysis can non-invasively detect diseases, with short-chain fatty acids (SCFAs) identified as key biomarkers. However, SCFA quantification is technically challenging due to chemical instability during thermal desorption (TD) tube analysis. Esterification with methanol may cause methyl ester formation, which impairs diagnostic sensitivity and reproducibility. We hypothesised that methanol-driven esterification of SCFAs is temperature- and time-dependent and can occur under common solvent handling and storage conditions used in TD-based analysis, even without the addition of acid or base catalyst. Here we show that methanol-driven SCFA esterification occurs in the liquid phase but not in the gas phase. Esterification rates increase with higher methanol-to-SCFA ratios and elevated temperatures. Furthermore, prolonged storage at higher temperatures accelerated SCFA esterification, reducing recovery by up to 70% after two months at room temperature and refrigerated conditions. Addressing these artefacts is crucial for ensuring the diagnostic accuracy of SCFA-based breath tests.
Date Issued
2026-05-27
Date Acceptance
2026-03-18
Citation
Communications Chemistry, 2026, 9 (1)
ISSN
2399-3669
Publisher
Nature Portfolio
Journal / Book Title
Communications Chemistry
Volume
9
Issue
1
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.nature.com/articles/s42004-026-01998-5
Publication Status
Published
Article Number
189
Date Publish Online
2026-04-01