{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T09:08:17Z","timestamp":1780304897166,"version":"3.54.0"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T00:00:00Z","timestamp":1774742400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003246","name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["KICH1.VE03.21.004"],"award-info":[{"award-number":["KICH1.VE03.21.004"]}],"id":[{"id":"10.13039\/501100003246","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":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Illicit amphetamine synthesis is frequently conducted using the well\u2010known Leuckart method, generating complex impurity profiles that provide forensic insights. This study reports the effect of reaction temperature and time during the first step of the Leuckart synthesis on subsequent conversion efficiency and impurity profile. Controlled syntheses were conducted at 120\u00b0C, 140\u00b0C, and 160\u00b0C, with samples collected at defined intervals. Reaction progress was monitored by gas chromatography\u2013flame ionization detection (GC\u2013FID), and impurity profiling followed the European harmonized method for profiling amphetamine (EHMPA) using GC\u2013mass spectrometry (GC\u2013MS). In addition, preparative liquid chromatography (prep\u2010LC) followed by LC\u2013high\u2010resolution MS (LC\u2013HRMS) was employed to isolate and characterize previously unidentified impurities. Results indicate that higher temperatures and longer reaction times accelerate benzyl methyl ketone (BMK) conversion, increasing the formation of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010formylamphetamine (after step 1) and amphetamine (after step 2). Lower temperatures and shorter reaction times result in incomplete conversion and the persistent presence of BMK, along with several impurities, including unsaturated ketones (3,5\u2010diphenyl\u20104\u2010methyl\u20103\u2010penten\u20102\u2010one and 1,5\u2010diphenyl\u20104\u2010methyl\u20103\u2010penten\u20102\u2010one), 1,3\u2010dimethyl\u20102\u2010phenylnaphthalene (Naphthalene 1), and 1\u2010benzyl\u20103\u2010methylnaphthalene (Naphthalene 2). Elevated temperatures favor the formation of 4\u2010methyl\u20105\u2010phenylpyrimidine (4M5PP), 4\u2010benzylpyrimidine (4BP),\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N\u2010<\/jats:italic>\n                    bis\u2010(\u20121\u2010phenylpropan\u20102\u2010yl)formamide (DPIF), and Unknowns A2, B1, and B2, which were tentatively identified as\n                    <jats:italic>N<\/jats:italic>\n                    \u2010[3,5\u2010diphenyl\u20104\u2010methyl\u20103\u2010penten\u20102\u2010yl]amine, and the\n                    <jats:italic>cis<\/jats:italic>\n                    \/\n                    <jats:italic>trans<\/jats:italic>\n                    isomers of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010[1,5\u2010diphenyl\u20104\u2010methyl\u20103\u2010penten\u20102\u2010yl]amine, respectively. These amines form via hydrolysis of\n                    <jats:italic>N<\/jats:italic>\n                    \u2010formylamino derivatives generated from unsaturated ketone intermediates. These findings demonstrate that reaction temperature and time strongly govern both amphetamine formation and impurity composition. The identified impurities serve as distinct chemical indicators, enabling reconstruction of illicit synthesis conditions and supporting intelligence on amphetamine production.\n                  <\/jats:p>","DOI":"10.1002\/dta.70063","type":"journal-article","created":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T05:47:16Z","timestamp":1774849636000},"page":"725-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effect of Reaction Time and Temperature on the Impurity Profile of Amphetamine in the Leuckart Method"],"prefix":"10.1002","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-9194-4506","authenticated-orcid":false,"given":"Maartje\u00a0C.\u00a0M.","family":"Verhoeven","sequence":"first","affiliation":[{"name":"Van't Hoff Institute for Molecular Science University of Amsterdam  Amsterdam the Netherlands"},{"name":"Netherlands Forensic Institute (NFI)  The Hague the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert\u00a0C.","family":"Huls","sequence":"additional","affiliation":[{"name":"Netherlands Forensic Institute (NFI)  The Hague the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly\u00a0W.","family":"van der Stelt","sequence":"additional","affiliation":[{"name":"Netherlands Forensic Institute (NFI)  The Hague the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelle\u00a0C.","family":"de Koning","sequence":"additional","affiliation":[{"name":"Van't Hoff Institute for Molecular Science University of Amsterdam  Amsterdam the Netherlands"},{"name":"Department of CBRN Protection TNO Defence Safety and Security  Rijswijk the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"van Grol","sequence":"additional","affiliation":[{"name":"Department of CBRN Protection TNO Defence Safety and Security  Rijswijk the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruben\u00a0F.","family":"Kranenburg","sequence":"additional","affiliation":[{"name":"Van't Hoff Institute for Molecular Science University of Amsterdam  Amsterdam the Netherlands"},{"name":"Unit National Expertise and Operations (LX), Domain R&amp;D, Innovation and Expertise (RiX), National Forensic Service Center The Netherlands Police  Driebergen the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arian\u00a0C.","family":"van Asten","sequence":"additional","affiliation":[{"name":"Van't Hoff Institute for Molecular Science University of Amsterdam  Amsterdam the Netherlands"},{"name":"Center for Forensic Science and Medicine Co van Ledden Hulsebosch Center (CLHC)  Amsterdam the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janneke\u00a0W.","family":"Hulshof","sequence":"additional","affiliation":[{"name":"Netherlands Forensic Institute (NFI)  The 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