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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.<\/jats:p>","DOI":"10.1038\/s42004-026-01998-5","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T12:57:17Z","timestamp":1775048237000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Methanol-driven esterification of volatile short-chain fatty acids in thermal desorption-based analysis"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2998-9807","authenticated-orcid":false,"given":"Philip Kwan Hung","family":"Leung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alson Hubert Kwongyiu","family":"Wong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiling","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungmin Jen","family":"Yoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Bajo-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3461-8891","authenticated-orcid":false,"given":"Valerio","family":"Converso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Parker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrik","family":"Spanel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George Bushra","family":"Hanna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8637-0285","authenticated-orcid":false,"given":"Ilaria","family":"Belluomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"1998_CR1","doi-asserted-by":"publisher","first-page":"034001","DOI":"10.1088\/1752-7163\/abf1d0","volume":"15","author":"N Drabi\u0144ska","year":"2021","unstructured":"Drabi\u0144ska, N. et al. A literature survey of all volatiles from healthy human breath and bodily fluids: the human volatilome. J. Breath. Res. 15, 034001 (2021).","journal-title":"J. Breath. Res."},{"key":"1998_CR2","doi-asserted-by":"crossref","unstructured":"de Lacy Costello, B. et al. A review of the volatiles from the healthy human body. J. Breath Res. 8, 014001\u20137155\/8\/1\/014001. Epub 2014 Jan 13 (2014).","DOI":"10.1088\/1752-7155\/8\/1\/014001"},{"key":"1998_CR3","doi-asserted-by":"crossref","unstructured":"Amann, A. et al. The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva. J. Breath Res. 8, 034001\u20137155\/8\/3\/034001 (2014).","DOI":"10.1088\/1752-7155\/8\/3\/034001"},{"key":"1998_CR4","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s44324-025-00066-1","volume":"3","author":"Jyoti","year":"2025","unstructured":"Jyoti & Dey, P. 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The remaining authors disclose no conflicts.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"189"}}