{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T10:14:19Z","timestamp":1783332859491,"version":"3.54.6"},"reference-count":16,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T00:00:00Z","timestamp":1723852800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC3300902"],"award-info":[{"award-number":["2022YFC3300902"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Testing and Analysis"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The effective implementation of drug precursor legislation has driven the innovation and design of new alternative substances. The application of 1,3\u2010dicarbonyl precursors as alternative precursors for the synthesis of 1\u2010phenyl\u20102\u2010propanone (P2P) and 3,4\u2010methylenedioxyphenyl\u20102\u2010propanone (MDP2P) has created new challenges to legal control. Their 1,3\u2010dicarbonyl structure allows the precursors to exist as an equilibrium mixture of the tautomeric diketo and keto\u2010enolic forms during the nuclear magnetic resonance (NMR) analysis. In this study, the keto\u2010enol tautomerism of four 1,3\u2010dicarbonyl drug pre\u2010precursors, <jats:italic>\u03b1<\/jats:italic>\u2010phenylacetoacetamide (APAA), methyl <jats:italic>\u03b1<\/jats:italic>\u2010phenylacetoacetate (MAPA), ethyl \u03b1\u2010phenylacetoacetate (EAPA), and methyl 2\u2010(benzo[<jats:italic>d<\/jats:italic>][1,3]dioxol\u20105\u2010yl)\u20103\u2010oxobutanoate (MAMDPA) were investigated through NMR. One\u2010dimensional (1D) and 2D NMR were combined to assign signals for the diketo and keto\u2010enolic tautomers. Results showed that the keto\u2010enol tautomerism was solvent\u2010dependent but was also influenced by the substituent present in the molecule. Further, the analysis results indicated that majority of substances existed mainly in the diketo form. The enol\u2010keto equilibrium constant (<jats:italic>K<\/jats:italic><jats:sub><jats:italic>eq<\/jats:italic><\/jats:sub>) was stable in dimethyl sulfoxide\u2010<jats:italic>d<\/jats:italic><jats:sub>6<\/jats:sub> and chloroform\u2010<jats:italic>d<\/jats:italic>, while unstable for some compounds in acetone\u2010<jats:italic>d<\/jats:italic><jats:sub>6<\/jats:sub> and deuterated methanol. The presence of impurities in the seized sample may disrupt the equilibrium between keto\u2010enol tautomers in 1,3\u2010dicarbonyl precursors. After the optimization of several key quantitative parameters, a quantitative NMR method for the quantification of 1,3\u2010dicarbonyl drug precursors were also developed to facilitate their quantitative analysis. This is the first study to investigate the keto\u2010enol tautomerism and quantification of 1,3\u2010dicarbonyl drug precursors by NMR, providing a new approach for structure analysis and quantification of new precursor analogues.<\/jats:p>","DOI":"10.1002\/dta.3789","type":"journal-article","created":{"date-parts":[[2024,8,17]],"date-time":"2024-08-17T08:10:53Z","timestamp":1723882253000},"page":"850-857","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["An NMR study on the keto\u2010enol tautomerism of 1,3\u2010dicarbonyl drug precursors"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9914-8349","authenticated-orcid":false,"given":"Xue\u2010yan","family":"Liu","sequence":"first","affiliation":[{"name":"China Pharmaceutical University  China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Monitoring and Control Drug Intelligence and Forensic Center, Ministry of Public Security  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9779-3489","authenticated-orcid":false,"given":"Cui\u2010mei","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Monitoring and Control Drug Intelligence and Forensic Center, Ministry of Public Security  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen\u2010dong","family":"Hua","sequence":"additional","affiliation":[{"name":"Key Laboratory of Drug Monitoring and Control Drug Intelligence and Forensic Center, Ministry of Public Security  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,8,17]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).Drug precursor developments in the European Union. Accessed May 10 2024.https:\/\/www.emcdda.europa.eu\/publications\/emcdda-papers\/drug-precursor-developments-eu_en"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.3169"},{"key":"e_1_2_7_4_1","first-page":"33","article-title":"Impurity profiling\/comparative analyses of samples of 1\u2010phenyl\u20102\u2010propanone","author":"Krawczyk W","year":"2005","journal-title":"Bull Narc"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2014.12.021"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0379\u20100738(93)90238\u20106"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-458X(200007)38:7<512::AID-MRC664>3.0.CO;2-Z"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2006.05.036"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules25225441"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpca.6b08707"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1139\/v65\u2010202"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1070\/RC2002v071n12ABEH000727"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/jp9839910"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2009.12.040"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2022.111450"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.talanta.2023.124257"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnmrs.2010.05.001"}],"container-title":["Drug Testing and Analysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/dta.3789","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T22:52:50Z","timestamp":1760395970000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/dta.3789"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,8,17]]},"references-count":16,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,6]]}},"alternative-id":["10.1002\/dta.3789"],"URL":"https:\/\/doi.org\/10.1002\/dta.3789","archive":["Portico"],"relation":{},"ISSN":["1942-7603","1942-7611"],"issn-type":[{"value":"1942-7603","type":"print"},{"value":"1942-7611","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,8,17]]},"assertion":[{"value":"2024-05-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-08-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}