{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:27:13Z","timestamp":1792679233528,"version":"4.5.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:00:00Z","timestamp":1740614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Concentrations of amitriptyline and nortriptyline in postmortem blood samples may not accurately reflect the concentrations at the time of death due to postmortem redistribution or degradation. The brain is suggested as an alternative matrix since it is less subjected to postmortem redistribution and more protected against trauma and putrefaction, but reference concentrations in brain tissue are scarce. In this study, we aimed to provide concentrations in brain tissue and brain\u2013blood ratios in 53 postmortem cases, where amitriptyline and\/or nortriptyline were detected. To establish reference levels, each case was assigned to one of three classes according to the cause of death: (i) lethal intoxication by the sum of amitriptyline and nortriptyline or nortriptyline alone, (ii) lethal intoxication by the drugs in combination with other drugs, and (iii) the cause of death was not influenced by amitriptyline and\/or nortriptyline. A positive correlation between blood and brain concentrations was found with a Spearman coefficient of 0.98. In 42 cases, where both drugs were detected, the 10\u201390 percentiles in brain tissue ranged from 0.17\u20139.1\u2009mg\/kg (median: 0.78\u2009mg\/kg) for amitriptyline and 0.22\u20135.0\u2009mg\/kg (median: 1.43\u2009mg\/kg) for nortriptyline across all classes. In 11 cases where only nortriptyline was detected, the percentiles ranged from 0.32\u20137.2\u2009mg\/kg (median: 0.28\u2009mg\/kg) in brain tissue. A median brain\u2013blood ratio of 3.4 was found for amitriptyline, 8.5 for nortriptyline as a metabolite of amitriptyline and 9.7 for nortriptyline as an individual ingested drug. No significant difference was found between the different classes. The obtained brain concentrations and brain\u2013blood ratio can contribute to the alternative or complementary use of brain tissue for future toxicological investigations.<\/jats:p>","DOI":"10.1093\/jat\/bkaf017","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T21:21:06Z","timestamp":1741123266000},"page":"209-215","source":"Crossref","is-referenced-by-count":3,"title":["Brain concentrations and brain\u2013blood ratios of amitriptyline and nortriptyline in forensic postmortem cases"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-3987-6186","authenticated-orcid":false,"given":"Mikayla Zo\u00eb","family":"van der Meer","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8048-3222","authenticated-orcid":false,"given":"Brian Schou","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-5246","authenticated-orcid":false,"given":"Michael","family":"Nedahl","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5159-8549","authenticated-orcid":false,"given":"Marie Katrine Klose","family":"Nielsen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, Section of Forensic Chemistry, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen,","place":["Denmark"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,2,27]]},"reference":[{"key":"2025041701470758600_R1","article-title":"Depressive disorder (depression)","author":"World Health Organisation (WHO)","year":"2023"},{"key":"2025041701470758600_R2","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1017\/S0033291721003160","article-title":"Antidepressant use in low- middle- and high-income countries: a World Mental Health Surveys report","volume":"53","author":"Kazdin","year":"2023","journal-title":"Psychol Med"},{"key":"2025041701470758600_R3","doi-asserted-by":"publisher","first-page":"384","DOI":"10.2174\/1570159X19666210609161447","article-title":"Depression and pain: use of antidepressants","volume":"20","author":"Bonilla-Jaime","year":"2022","journal-title":"Curr Neuropharmacol"},{"key":"2025041701470758600_R4","doi-asserted-by":"publisher","DOI":"10.1016\/j.molliq.2023.123766","article-title":"Impact of pH and membrane nature on distribution and permeability processes of nortriptyline hydrochloride","volume":"394","author":"Volkova","year":"2024","journal-title":"J Mol Liq"},{"key":"2025041701470758600_R5","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/s12024-018-0041-4","article-title":"Toxicological findings in suicides \u2013 frequency of antidepressant and antipsychotic substances","volume":"15","author":"Methling","year":"2019","journal-title":"Forensic Sci, Med Pathol"},{"key":"2025041701470758600_R6","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.jflm.2012.02.010","article-title":"Postmortem drug concentration intervals for the non-intoxicated state \u2013 a review","volume":"19","author":"Linnet","year":"2012","journal-title":"J Forensic Leg Med"},{"key":"2025041701470758600_R7","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/0379-0738(94)90241-0","article-title":"Postmortem release of amitriptyline from the lungs; 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