{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T15:40:01Z","timestamp":1773934801141,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"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":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Detomidine, 5\u2010[(2,3\u2010dimethylphenyl)methyl]\u20101\n                    <jats:italic>H<\/jats:italic>\n                    \u2010imidazole, is a tranquilizer\/sedative\/analgesic widely used in equine medicine and regulated by several different analyte concentrations of detomidine and its hydroxydetomidine and carboxydetomidine metabolites in plasma and urine. Accurate regulatory quantitation of detomidine at low picogram\/mL concentrations requires the availability of a stable isotope internal standard of detomidine; however, to the best of our knowledge, no certified deuterated internal standard of detomidine is commercially available and its synthesis has not been reported. Here, we report the first synthesis and characterization of detomidine\u2010\n                    <jats:italic>d<\/jats:italic>\n                    , prepared in six sequential steps consisting of a deuterium\u2013hydrogen exchange, diazotization, Grignard coupling, hydrogenolysis, and palladium\u2010catalyzed deuterium\u2013hydrogen exchange. This overall route gave detomidine\u2010\n                    <jats:italic>d<\/jats:italic>\n                    in moderate chemical yield with each intermediate purified to &gt;\u200990% purity as determined by RP\u2010HPLC. Regiochemistry and isotopic enrichment were confirmed by\n                    <jats:sup>1<\/jats:sup>\n                    H NMR and LC\/MS, demonstrating a viable method for the incorporation of three deuterium atoms into the detomidine scaffold. This internal standard will allow for precise LC\/MS quantitation of detomidine at regulatory threshold concentrations, enabling accurate detection and quantitation of picogram\/mL concentrations in equine blood and urine samples, thereby supporting regulatory compliance for equine medication control programs.\n                  <\/jats:p>","DOI":"10.1002\/jlcr.70023","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:11:51Z","timestamp":1773756711000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Characterization of Deuterated Detomidine for Use in Equine Medication Regulation"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9977-3633","authenticated-orcid":false,"given":"Justin\u00a0C.","family":"Holmes","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3076-264X","authenticated-orcid":false,"given":"Adedamola\u00a0S.","family":"Arojojoye","sequence":"additional","affiliation":[{"name":"Department of Chemistry University of Kentucky  Lexington Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4947-7283","authenticated-orcid":false,"given":"Samuel\u00a0G.","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":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodney","family":"Eisenberg","sequence":"additional","affiliation":[{"name":"Frontier BioPharm, LLC  Richmond Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6234-3197","authenticated-orcid":false,"given":"Clara\u00a0K.","family":"Fenger","sequence":"additional","affiliation":[{"name":"Equine Integrated Medicine  Georgetown Kentucky USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1967-5451","authenticated-orcid":false,"given":"George\u00a0A.","family":"Maylin","sequence":"additional","affiliation":[{"name":"New York Drug Testing and Research Program  Ithaca New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kimberly","family":"Brewer","sequence":"additional","affiliation":[{"name":"Consulting Toxicologist  Wellington Florida USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014\u20102999(85)90721\u20106"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20103306.1986.tb03655.x"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.2746\/042516409X370900"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2460\/ajvr.72.10.1378"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.21836\/PEM20220607"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20103306.1988.tb01535.x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF03189930"},{"key":"e_1_2_11_9_1","unstructured":"Frontier BioPharm. Accessed October 2 2025 https:\/\/frontierbiopharm.com\/product.html."},{"issue":"2","key":"e_1_2_11_10_1","first-page":"263","article-title":"Immunoassay Detection of Drugs in Racing Horses. IX. Detection of Detomidine in Equine Blood and Urine by Radioimmunoassay","volume":"63","author":"Wood T.","year":"1989","journal-title":"Research Communications in Chemical Pathology and Pharmacology"},{"key":"e_1_2_11_11_1","unstructured":"S. D.Stanley J. M.Yang T. W.Wood et\u00a0al. \u201cDetomidine Clearance in the Horse as Determined by ELISA \u201d inProceedings of the 9th International Conference of Racing Analysts and Veterinarians(1992):193\u2013197."},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.58502\/DTT.24.0002"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.2580140405"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200701147"},{"key":"e_1_2_11_15_1","unstructured":"Association of Racing Commissioners International (ARCI) \u201cUniform Classification Guidelines for Foreign Substances and Recommended Penalties and Model Rule \u201d Version 17.0 accessed October 2 2025 https:\/\/www.arci.com\/docs\/Uniform\u2010Classification\u2010Guidelines\u2010Version\u201017.0.pdf."},{"key":"e_1_2_11_16_1","unstructured":"Racing Medication and Testing Consortium (RMTC) \u201cDetomidine Monograph \u201d accessed October 2 2025 https:\/\/rmtcnet.com\/wp\u2010content\/uploads\/2020\u201010\u2010Detomidine\u2010Monograph\u2010FINAL.pdf."},{"key":"e_1_2_11_17_1","unstructured":"Horseracing Integrity and Safety Authority (HISA) \u201cRegulations \u201d accessed October 2 2025 https:\/\/hisaus.org\/regulations."},{"key":"e_1_2_11_18_1","unstructured":"International Federation of Horseracing Authorities (IFHA) \u201cInternational Agreement on Breeding Racing and Wagering \u201d accessed October 2 2025 https:\/\/www.ifhaonline.org\/default.asp?section=IABRW&area=18."}],"container-title":["Journal of Labelled Compounds and Radiopharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jlcr.70023","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jlcr.70023","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jlcr.70023","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T13:30:26Z","timestamp":1773927026000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/jlcr.70023"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3]]},"references-count":17,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,3]]}},"alternative-id":["10.1002\/jlcr.70023"],"URL":"https:\/\/doi.org\/10.1002\/jlcr.70023","archive":["Portico"],"relation":{},"ISSN":["0362-4803","1099-1344"],"issn-type":[{"value":"0362-4803","type":"print"},{"value":"1099-1344","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3]]},"assertion":[{"value":"2025-11-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70023"}}