{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T12:10:44Z","timestamp":1788610244914,"version":"build-2803163510"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,5,9]],"date-time":"2020-05-09T00:00:00Z","timestamp":1588982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The analgesics, codeine, fentanyl, oxycodone and tramadol, frequently occur in postmortem cases and determining their role in the cause of death can be challenging. However, postmortem blood is susceptible to redistribution and may not be available in cases of severe blood loss, putrefaction or burns. Brain tissue may serve as a viable supplement to blood or on its own, as it is resistant to postmortem redistribution and often available as a sample matrix when blood is not available. We present brain and blood concentrations and brain\u2013blood ratios of the four analgesics from 210 autopsy cases. The cases were classified according to the presumed cause of death: A: The compound was believed to have solely caused a fatal intoxication. B: The compound was assumed to have contributed to a fatal outcome in combination with other drugs, alcohol or disease. C: The compound was not regarded as being related to the cause of death. Blood and brain samples were prepared by automatic solid phase extraction and quantified by liquid chromatography\u2013mass spectrometry. The squared correlation coefficients between concentrations in brain tissue and blood ranged 0.45\u20130.91. The median brain\u2013blood ratios were codeine 1.8 (range 0.47\u20134.6), fentanyl 2.1 (range 0.29\u201316), oxycodone 1.8 (range 0.11\u20136.0) and tramadol 1.8 (range 0.047\u20136.8). A significantly higher brain\u2013blood ratio of codeine was observed in cases where heroin had been administered, although there was a wide overlap. Intravenous and transdermal fentanyl administration could not be distinguished based on the blood or brain concentration or the brain\u2013blood ratio. The results of this study may benefit the toxicological investigation in postmortem cases where one of the four analgesics are suspected of having contributed to or caused a fatal intoxication.<\/jats:p>","DOI":"10.1093\/jat\/bkaa048","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T07:08:47Z","timestamp":1588662527000},"page":"53-59","source":"Crossref","is-referenced-by-count":15,"title":["Postmortem Brain\u2013Blood Ratios of Codeine, Fentanyl, Oxycodone and Tramadol"],"prefix":"10.1093","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-5246","authenticated-orcid":false,"given":"Michael","family":"Nedahl","sequence":"first","affiliation":[{"name":"Department of Forensic Medicine, University of Copenhagen, Section of Forensic Chemistry, Frederik V\u2019s vej 11, 3. Floor, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sys Stybe","family":"Johansen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, University of Copenhagen, Section of Forensic Chemistry, Frederik V\u2019s vej 11, 3. Floor, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristian","family":"Linnet","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, University of Copenhagen, Section of Forensic Chemistry, Frederik V\u2019s vej 11, 3. Floor, 2100 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,9]]},"reference":[{"key":"2021020912453700700_ref1","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.forsciint.2015.01.003","article-title":"Fatal poisoning in drug addicts in the Nordic countries in 2012","volume":"248","author":"Simonsen","year":"2015","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref2","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1093\/bja\/81.1.58","article-title":"Opioid tolerance: the clinical perspective","volume":"81","author":"Collett","year":"1998","journal-title":"British Journal of Anaesthesia"},{"key":"2021020912453700700_ref3","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.neuropharm.2017.10.016","article-title":"Fentanyl, fentanyl analogs and novel synthetic opioids: a comprehensive review","volume":"134","author":"Armenian","year":"2018","journal-title":"Neuropharmacology"},{"key":"2021020912453700700_ref4","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.15585\/mmwr.mm655051e1","article-title":"Increases in drug and opioid-involved overdose deaths\u2014United States, 2010\u20132015","volume":"65","author":"Rudd","year":"2016","journal-title":"Morbidity and Mortality Weekly Report"},{"key":"2021020912453700700_ref5","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.jflm.2012.02.010","article-title":"Postmortem drug concentration intervals for the non-intoxicated state - a review","volume":"19","author":"Linnet","year":"2012","journal-title":"Journal of Forensic and Legal Medicine"},{"key":"2021020912453700700_ref6","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0379-0738(90)90182-X","article-title":"Post-mortem drug redistribution - a toxicological nightmare","volume":"45","author":"Pounder","year":"1990","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref7","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1007\/s12024-012-9341-2","article-title":"The effect of the postmortem interval on the redistribution of drugs: a comparison of mortuary admission and autopsy blood specimens","volume":"8","author":"Gerostamoulos","year":"2012","journal-title":"Forensic Science, Medicine, and Pathology"},{"key":"2021020912453700700_ref8","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1309\/AJCP4X5VHFSOERFT","article-title":"Postmortem redistribution of fentanyl in blood","volume":"133","author":"Olson","year":"2010","journal-title":"American Journal of Clinical Pathology"},{"key":"2021020912453700700_ref9","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1093\/jat\/bku139","article-title":"Brain tissue: a viable postmortem toxicological specimen","volume":"39","author":"Rohrig","year":"2015","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref10","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1016\/j.forsciint.2019.06.007","article-title":"Brain-blood ratio of morphine in heroin and morphine autopsy cases","volume":"301","author":"Nedahl","year":"2019","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref11","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/dta.2359","article-title":"Validation of a fully automated solid-phase extraction and ultra-high-performance liquid chromatography-tandem mass spectrometry method for quantification of 30 pharmaceuticals and metabolites in post-mortem blood and brain samples","volume":"10","author":"Nielsen","year":"2018","journal-title":"Drug Testing and Analysis"},{"key":"2021020912453700700_ref12","doi-asserted-by":"crossref","first-page":"2607","DOI":"10.1007\/s00216-012-6670-7","article-title":"Quantification of 31 illicit and medicinal drugs and metabolites in whole blood by fully automated solid-phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry","volume":"405","author":"Bj\u00f8rk","year":"2013","journal-title":"Analytical and Bioanalytical Chemistry"},{"key":"2021020912453700700_ref13","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1002\/dta.2120","article-title":"Targeted and non-targeted drug screening in whole blood by UHPLC-TOF-MS with data-independent acquisition","volume":"9","author":"Mollerup","year":"2017","journal-title":"Drug Testing and Analysis"},{"key":"2021020912453700700_ref14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1520\/JFS14071J","article-title":"A compilation of fatal and control concentrations of drugs in postmortem femoral blood","volume":"42","author":"Druid","year":"1997","journal-title":"Journal of Forensic Sciences"},{"key":"2021020912453700700_ref15","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/jat\/bkx098","article-title":"Reference brain\/blood concentrations of citalopram, duloxetine, mirtazapine and sertraline","volume":"42","author":"Nedahl","year":"2018","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref16","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.forsciint.2016.02.051","article-title":"Post-mortem levels and tissue distribution of codeine, codeine-6-glucuronide, norcodeine, morphine and morphine glucuronides in a series of codeine-related deaths","volume":"262","author":"Frost","year":"2016","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref17","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1093\/jat\/bku016","article-title":"Unexpected variation of the codeine\/morphine ratio following fatal heroin overdose","volume":"38","author":"Gambaro","year":"2014","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref18","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1093\/jat\/30.8.603","article-title":"Fentanyl-related deaths in Ontario, Canada: toxicological findings and circumstances of death in 112 cases (2002-2004)","volume":"30","author":"Martin","year":"2006","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref19","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1111\/j.1556-4029.2007.00597.x","article-title":"Oral abuse of fentanyl patches (Duragesic\u00ae): seven case reports","volume":"53","author":"Woodall","year":"2008","journal-title":"Journal of Forensic Sciences"},{"key":"2021020912453700700_ref20","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1002\/dta.2655","article-title":"Summary statistics for drug concentrations in post-mortem femoral blood representing all causes of death","volume":"11","author":"Ketola","year":"2019","journal-title":"Drug Testing and Analysis"},{"key":"2021020912453700700_ref21","doi-asserted-by":"publisher","first-page":"109999","DOI":"10.1016\/j.forsciint.2019.109999","article-title":"Distribution of synthetic opioids in postmortem blood, vitreous humor and brain","volume":"305","author":"Chesser","year":"2019","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.forsciint.2015.10.021","article-title":"Postmortem tissue distribution of acetyl fentanyl, fentanyl and their respective nor-metabolites analyzed by ultrahigh performance liquid chromatography with tandem mass spectrometry","volume":"257","author":"Poklis","year":"2015","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref23","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1007\/s11419-013-0216-3","article-title":"Fentanyl: cause of death or incidental finding? Postmortem peripheral blood concentrations with and without documented transdermal patch use","volume":"32","author":"Lung","year":"2014","journal-title":"Forensic Toxicology"},{"key":"2021020912453700700_ref24","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.forsciint.2018.07.020","article-title":"Postmortem analysis of three methoxyacetylfentanyl-related deaths in Denmark and in vitro metabolite profiling in pooled human hepatocytes","volume":"290","author":"Mardal","year":"2018","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref25","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1093\/jat\/33.8.423","article-title":"Oxycodone-related fatalities in the West of Scotland","volume":"33","author":"Al-Asmari","year":"2009","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref26","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1016\/j.forsciint.2016.08.015","article-title":"Post-mortem concentrations of drugs determined in femoral blood in single-drug fatalities compared with multi-drug poisoning deaths","volume":"267","author":"Jones","year":"2016","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref27","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1520\/JFS2004019","article-title":"Tramadol (Ultram) concentrations in death investigation and impaired driving cases and their significance","volume":"49","author":"Clarkson","year":"2004","journal-title":"Journal of Forensic Sciences"},{"key":"2021020912453700700_ref28","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1093\/jat\/34.9.599","article-title":"Quantification in postmortem blood and identification in urine of tramadol and its two main metabolites in two cases of lethal tramadol intoxication","volume":"34","author":"De Backer","year":"2010","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref29","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/jat\/21.7.529","article-title":"Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers","volume":"21","author":"Goeringer","year":"1997","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref30","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1093\/jat\/14.6.385","article-title":"A death due to self-administered fentanyl","volume":"14","author":"Chaturvedi","year":"1990","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref31","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/S0379-0738(03)00134-8","article-title":"The incidence of drugs in drivers killed in Australian road traffic crashes","volume":"134","author":"Drummer","year":"2003","journal-title":"Forensic Science International"},{"key":"2021020912453700700_ref32","doi-asserted-by":"crossref","first-page":"457","DOI":"10.3109\/15563657508990077","article-title":"Blood codeine concentrations in fatalities associated with codeine","volume":"8","author":"Wright","year":"1975","journal-title":"Clinical Toxicology"},{"key":"2021020912453700700_ref33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1520\/JFS2004194","article-title":"One hundred seventry two deaths involving the use of oxycodone in palm beach county","volume":"50","author":"Wolf","year":"2005","journal-title":"Journal of Forensic Science"},{"key":"2021020912453700700_ref34","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1093\/jat\/32.8.673","article-title":"Free oxycodone concentrations in 67 postmortem cases from the hennepin county medical examiner\u2019s office","volume":"32","author":"Thompson","year":"2008","journal-title":"Journal of Analytical Toxicology"},{"key":"2021020912453700700_ref35","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1520\/JFS13685J","article-title":"A study of deaths involving oxycodone","volume":"39","author":"Drummer","year":"1994","journal-title":"Journal of Forensic Sciences"}],"container-title":["Journal of Analytical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jat\/advance-article-pdf\/doi\/10.1093\/jat\/bkaa048\/33678452\/bkaa048.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jat\/article-pdf\/45\/1\/53\/36218330\/bkaa048.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jat\/article-pdf\/45\/1\/53\/36218330\/bkaa048.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,8,5]],"date-time":"2024-08-05T04:17:24Z","timestamp":1722831444000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jat\/article\/45\/1\/53\/5835192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,9]]},"references-count":35,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,5,9]]},"published-print":{"date-parts":[[2021,2,6]]}},"URL":"https:\/\/doi.org\/10.1093\/jat\/bkaa048","relation":{},"ISSN":["0146-4760","1945-2403"],"issn-type":[{"value":"0146-4760","type":"print"},{"value":"1945-2403","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,1,1]]},"published":{"date-parts":[[2020,5,9]]}}}