{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:48:22Z","timestamp":1792176502403,"version":"4.4.0"},"reference-count":14,"publisher":"Wiley","issue":"10-11","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":31,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100005825","name":"National Institute of Food and Agriculture","doi-asserted-by":"publisher","award":["KY014066"],"award-info":[{"award-number":["KY014066"]}],"id":[{"id":"10.13039\/100005825","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Acetylpromazine, 1\u2010{10\u2010[3\u2010(dimethylamino)propyl]\u201010\n                    <jats:italic>H<\/jats:italic>\n                    \u2010phenothiazin\u20102\u2010yl}ethenone, C\n                    <jats:sub>19<\/jats:sub>\n                    H\n                    <jats:sub>22<\/jats:sub>\n                    N\n                    <jats:sub>2<\/jats:sub>\n                    OS, 326.46\u2009g\u00b7mol\n                    <jats:sup>\u22121<\/jats:sup>\n                    is a phenothiazine derivative at one time used in human medicine as an antipsychotic medication but now predominantly used in veterinary medicine as a sedative\/tranquilizer and referred to as acepromazine. In performance horses its use is regulated by using a 10\u2009ng\/mL threshold for the major urinary metabolite 2\u2010(1\u2010hydroxyethyl) promazine\u2010sulfoxide (HEPS) in equine urine. To enable accurate quantitation of HEPS in equine urine we have synthesized and purified hydroxyethylpromazine sulfoxide\u2010\n                    <jats:italic>d<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>4<\/jats:italic>\n                    <\/jats:sub>\n                    (HEPS\u2010\n                    <jats:italic>d<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>4<\/jats:italic>\n                    <\/jats:sub>\n                    ) to be used as a stable isotopically labeled internal standard. Although labeled HEPS is commercially available (CAS 1346605\u201030\u20108), to the best of our knowledge there is no published synthetic procedure in the scientific literature. Here we demonstrate a viable synthetic procedure consisting of four major steps: (i) freebasing the Acepromazine maleate salt, (ii) H\u2010D exchange of Acepromazine at room temperature, (iii) reduction of the ketone with NaBD\n                    <jats:sub>4<\/jats:sub>\n                    , and (iv) oxidation of the thioether via hydrogen peroxide and acetic acid. This deuterated internal standard will allow for precise LC\/MS quantitation of HEPS at regulatory threshold concentrations, enabling accurate detection and quantitation of picogram\/mL concentrations in equine urine samples, thereby supporting regulatory compliance for equine medication control programs.\n                  <\/jats:p>","DOI":"10.1002\/jlcr.70036","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T08:32:55Z","timestamp":1788251575000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Characterization of 2\u2010(1\u2010Hydroxyethyl)Promazine Sulfoxide\u2010\n                    <i>d<\/i>\n                    <sub>\n                      <i>4<\/i>\n                    <\/sub>\n                    HCl as an Internal Standard for the Accurate Quantitation of 2\u2010(1\u2010Hydroxyethyl)Promazine Sulfoxide in Equine Urine"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9977-3633","authenticated-orcid":false,"given":"Justin C.","family":"Holmes","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ballard C.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-7283","authenticated-orcid":false,"given":"Samuel G.","family":"Awuah","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Kentucky  Lexington Kentucky USA"},{"name":"Center for Pharmaceutical Research and Innovation, College of Pharmacy and Department of Pharmaceutical Sciences, College of Pharmacy University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodney","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Frontier BioPharm, LLC  Richmond Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1304-5684","authenticated-orcid":false,"given":"Andreas F.","family":"Lehner","sequence":"additional","affiliation":[{"name":"MSU Veterinary Diagnostic Laboratory, Section of Toxicology Michigan State University  Lansing Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-3197","authenticated-orcid":false,"given":"Clara K.","family":"Fenger","sequence":"additional","affiliation":[{"name":"Equine Integrated Medicine  Georgetown Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1967-5451","authenticated-orcid":false,"given":"George A.","family":"Maylin","sequence":"additional","affiliation":[{"name":"New York Drug Testing and Research Program  Ithaca New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberly","family":"Brewer","sequence":"additional","affiliation":[{"name":"Wellington Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8506-3147","authenticated-orcid":false,"given":"Thomas","family":"Tobin","sequence":"additional","affiliation":[{"name":"The Department of Veterinary Science and the Maxwell H. Gluck Equine Research Center, Martin\u2010Gatton College of Agriculture, Food and Environment and the Department of Toxicology and Cancer Biology University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13181\u2010014\u20100416\u20101"},{"key":"e_1_2_11_3_1","volume-title":"Drugs and the Performance Horse","author":"Tobin T.","year":"1981"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102885.1982.tb00495.x"},{"key":"e_1_2_11_5_1","first-page":"231","article-title":"Evaluation of Threshold Doses of Drug Action in the Horse Using Hematocrit Values as an Indicator","volume":"75","author":"Wood T.","year":"1992","journal-title":"Research Communications in Chemical Pathology and Pharmacology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvp.12494"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10337\u2010012\u20102234\u20104"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tvjl.2012.03.017"},{"key":"e_1_2_11_9_1","unstructured":"RMTC CTS \u201cMonograph Series: Acepromazine \u201d (2020) https:\/\/rmtcnet.com\/wp\u2010content\/uploads\/2020\u201010\u2010Acepromazine\u2010Monograph\u2010FINAL.pdf."},{"key":"e_1_2_11_10_1","unstructured":"Federal Trade Commission \u201cHISA Anti\u2010Doping and Medication Control Rule \u201d (2023) https:\/\/www.federalregister.gov\/documents\/2023\/01\/26\/2023\u201000957\/hisa\u2010anti\u2010doping\u2010and\u2010medication\u2010control\u2010rule."},{"key":"e_1_2_11_11_1","unstructured":"RMTC \u201cWithdrawal Guidance Advisory \u201d (2023) https:\/\/rmtcnet.com\/wp\u2010content\/uploads\/2023\/04\/2023\u201003.24\u2010RMTC\u2010Withdrawal\u2010Guidance\u2010of\u2010ADMC_UPDATED.pdf."},{"key":"e_1_2_11_12_1","volume-title":"Personal Communication to T Tobin","author":"Holloway K.","year":"2026"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20103306.1977.tb03978.x"},{"key":"e_1_2_11_14_1","volume-title":"World Rules for Equine Drug Testing and Therapeutic Medication Regulation: 2012 Policy of the National Horsemen's Benevolent and Protective Association, Inc","author":"Tobin T.","year":"2012"},{"key":"e_1_2_11_15_1","unstructured":"\u201cFrontier BioPharm \u201d Accessed May 28 2026 https:\/\/frontierbiopharm.com\/product.html."}],"container-title":["Journal of Labelled Compounds and Radiopharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jlcr.70036","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jlcr.70036","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jlcr.70036","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T18:07:01Z","timestamp":1792174021000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jlcr.70036"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8]]},"references-count":14,"journal-issue":{"issue":"10-11","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1002\/jlcr.70036"],"URL":"https:\/\/doi.org\/10.1002\/jlcr.70036","archive":["Portico"],"relation":{},"ISSN":["0362-4803","1099-1344"],"issn-type":[{"value":"0362-4803","type":"print"},{"value":"1099-1344","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8]]},"assertion":[{"value":"2026-06-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-20","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70036"}}