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For heroin, which effects are mainly mediated by the metabolites 6\u2010acetylmorphine (6\u2010AM; also known as 6\u2010monoacetylmorphine or 6\u2010MAM) and morphine, the optimal antibody specificity has been discussed. In rodents, 6\u2010AM specific antibodies have been recommended based on the rapid metabolism of heroin to 6\u2010AM in the bloodstream. Since the metabolic rate of heroin in blood is unsettled in humans, we examined heroin metabolism with state\u2010of\u2013the\u2010art analytical methodology (UHPLC\u2013MS\/MS) in freshly drawn human whole blood incubated with a wide range of heroin concentrations (1\u2013500\u2009\u03bcM). The half\u2010life of heroin was highly concentration dependent, ranging from 1.2\u20131.7\u2009min for concentrations at or above 25\u2009\u03bcM, and gradually increasing to approximately 20\u2009min for 1\u2009\u03bcM heroin. At concentrations that can be attained in the bloodstream shortly after an i.v. injection, approximately 70% was transformed into 6\u2010AM within 3\u2009min, similar to previous observations in vivo. Our results indicate that blood enzymes play a more important role for the rapid metabolism of heroin in humans than previously assumed. This points to 6\u2010AM as an important target for an efficient immunotherapeutic approach to block heroin effects in humans.<\/jats:p>","DOI":"10.1111\/bcpt.13926","type":"journal-article","created":{"date-parts":[[2023,7,15]],"date-time":"2023-07-15T08:28:22Z","timestamp":1689409702000},"page":"418-427","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Heroin metabolism in human blood and its impact for the design of an immunotherapeutic approach against heroin effects"],"prefix":"10.1111","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2877-0624","authenticated-orcid":false,"given":"Inger Lise","family":"Bogen","sequence":"first","affiliation":[{"name":"Section for Drug Abuse Research, Department of Forensic Sciences Oslo University Hospital  Oslo Norway"},{"name":"Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, Faculty of Mathematics and Natural Sciences University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6925-5130","authenticated-orcid":false,"given":"Fernando","family":"Boix","sequence":"additional","affiliation":[{"name":"Section for Drug Abuse Research, Department of Forensic Sciences Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8425-9743","authenticated-orcid":false,"given":"Jannike M\u00f8rch","family":"Andersen","sequence":"additional","affiliation":[{"name":"Section for Drug Abuse Research, Department of Forensic Sciences Oslo University Hospital  Oslo Norway"},{"name":"Section for Pharmacology and Pharmaceutical Biosciences, Department of Pharmacy, Faculty of Mathematics and Natural Sciences University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Synne","family":"Steinsland","sequence":"additional","affiliation":[{"name":"Section for Drug Abuse Research, Department of Forensic Sciences Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Nerem","sequence":"additional","affiliation":[{"name":"Section for Drug Abuse Research, Department of Forensic Sciences Oslo University Hospital  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7350-8778","authenticated-orcid":false,"given":"J\u00f8rg","family":"M\u00f8rland","sequence":"additional","affiliation":[{"name":"Division of Health Data and Digitalisation Norwegian Institute of Public Health  Oslo Norway"},{"name":"Institute of Clinical Medicine, Faculty of Medicine University of Oslo  Oslo Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"e_1_2_9_2_1","volume-title":"World drug report","author":"UNODC","year":"2022"},{"key":"e_1_2_9_3_1","volume-title":"International standards for the treatment of drug use disorders: revised edition incorporating results of field\u2010testing","year":"2020"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2010.10.001"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2012.07.011"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.forsciint.2012.11.010"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1159\/000501931"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(17)32812\u2010X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.11.190"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024\u20103205(83)90616\u20101"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006\u20102952(01)00689\u2010x"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.109.152462"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.113.212035"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145714000169"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.116.233510"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1067\/mcp.2001.117981"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010200645040\u201000005"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742\u20107843.2006.pto_233.x"},{"key":"e_1_2_9_19_1","first-page":"25","article-title":"Metabolism of heroin and its pharmacologic implications. 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