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As a fast-acting acetylcholinesterase inhibitor, aldicarb interferes with the nervous system by preventing the breakdown of acetylcholine. Aldicarb could be used as a chemical-warfare agent to cause mass casualty incidents. There is no specific FDA-approved medication for aldicarb detoxification. Our previous study revealed that an Fc-fused butyrylcholinesterase (BChE) mutant, known as CocH3-Fc(M3), can be inhibited rapidly by aldicarb and that the aldicarb-inhibited enzyme CocH3-Fc(M3) can be reactivated spontaneously, suggesting that CocH3-Fc(M3) may hydrolyze aldicarb. However, the suggested CocH3-Fc(M3)-catalyzed hydrolysis of aldicarb was not confirmed experimentally in the previous study. In the present study, by developing an LC-MS\/MS method to detect and quantify aldicarb and aldicarb oxime concentrations, we were able to directly observe the CocH3-Fc(M3)-catalyzed aldicarb hydrolysis for the first time, confirming that CocH3-Fc(M3) indeed has the desirable catalytic activity for aldicarb hydrolysis and may be considered as the first aldicarb hydrolase identified so far. Further, we carried out Michaelis\u2013Menten kinetic analysis on the CocH3-Fc(M3)-catalyzed aldicarb hydrolysis and determined the catalytic parameters (kcat\u00a0=\u00a00.060\u00a0min\u22121, KM\u00a0=\u00a02.5\u00a0\u03bcM, and kcat\/KM\u00a0=\u00a02.4\u00a0\u00d7\u00a0104 min\u22121 M\u22121) at 37\u00b0C. The obtained kinetic parameters at 37\u00b0C will be valuable for further in vivo studies and translational research using CocH3-Fc(M3) and for designing more potent enzymes to hydrolyze aldicarb in the future. Additionally, the LC-MS\/MS method developed in this study may serve as a valuable tool to accurately detect aldicarb and its reaction products in future food and environmental safety control efforts and aldicarb-related toxicology studies.<\/jats:p>","DOI":"10.1042\/bsr20254091","type":"journal-article","created":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T08:34:53Z","timestamp":1771576493000},"update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Observation of aldicarb hydrolysis by a cocaine hydrolase"],"prefix":"10.1042","volume":"46","author":[{"given":"Johnathan\u00a0E.","family":"LeSaint","sequence":"first","affiliation":[{"name":"1Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."},{"name":"2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel\u00a0J.","family":"Peter","sequence":"additional","affiliation":[{"name":"1Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."},{"name":"2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huimei","family":"Wei","sequence":"additional","affiliation":[{"name":"2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shawn","family":"Park","sequence":"additional","affiliation":[{"name":"2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4128-7269","authenticated-orcid":false,"given":"Chang-Guo","family":"Zhan","sequence":"additional","affiliation":[{"name":"1Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."},{"name":"2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8571-3744","authenticated-orcid":false,"given":"Fang","family":"Zheng","sequence":"additional","affiliation":[{"name":"1Molecular Modeling and Biopharmaceutical Center, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."},{"name":"2Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, 789 South Limestone Street, Lexington, KY 40536, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","published-online":{"date-parts":[[2026,4,22]]},"reference":[{"key":"2026042201364083300_B1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/B0-12-369400-0\/00038-7","volume-title":"Aldicarb, in Encyclopedia of Toxicology","author":"Harp","year":"2005","edition":"Second Edition"},{"key":"2026042201364083300_B2","doi-asserted-by":"publisher","first-page":"260","DOI":"10.1124\/jpet.123.002040","article-title":"Progress and challenges in developing medical countermeasures for chemical, biological, radiological, and nuclear threat agents","volume":"388","author":"Reddy","year":"2024","journal-title":"J. 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