{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T15:45:19Z","timestamp":1765295119741},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T00:00:00Z","timestamp":1580860800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,4,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Psychotropic drugs are regularly present in cases of sudden, unexpected death. Such drugs also tend to express significant postmortem redistribution. To facilitate further investigation of this phenomenon, reliable quantitative methods applicable to multiple biological matrices are needed. We present a validated ultra-performance liquid chromatography\u2013tandem mass spectrometry method for the simultaneous quantification of quetiapine, clozapine and mirtazapine in postmortem whole blood, skeletal muscle, brain tissue and liver tissue using high-performance liquid chromatography\u2013tandem mass spectrometry. Sample preparation was performed using liquid\u2013liquid extraction. The validated ranges were 3.8\u20131534, 16\u20131960 and 13\u20131060\u00a0\u03bcg\/L for quetiapine, clozapine and mirtazapine, respectively. Within-run and between-run accuracy (87.4\u2013122%) and precision (CV 1.5\u20138.9%), matrix effects (95\u2013101%) and recovery (35.7\u201392%) were validated at two concentration levels; 5.8 and 1227\u00a0\u03bcg\/L for quetiapine, 25 and 1568\u00a0\u03bcg\/L for clozapine and 20 and 849\u00a0\u03bcg\/L for mirtazapine. Stability in a 10\u00b0C environment was assessed for treated samples of brain, liver and muscle tissue, showing deviations in analyte concentrations ranging from \u22128% to 9% after 3\u00a0days. The analyte concentrations in treated samples of whole blood stored at 4\u00b0C deviated by &amp;lt;5% after 5\u00a0days. The method was applied in three forensic autopsy cases implicating quetiapine, clozapine and mirtazapine, respectively, in supratherapeutic concentrations.<\/jats:p>","DOI":"10.1093\/jat\/bkaa002","type":"journal-article","created":{"date-parts":[[2020,1,30]],"date-time":"2020-01-30T12:11:32Z","timestamp":1580386292000},"page":"440-448","source":"Crossref","is-referenced-by-count":12,"title":["A Validated Method for the Simultaneous Determination of Quetiapine, Clozapine and Mirtazapine in Postmortem Blood and Tissue Samples"],"prefix":"10.1093","volume":"44","author":[{"given":"H\u00e5vard","family":"Breivik","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trine N","family":"L\u00f8kken","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Sl\u00f8rdal","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway"},{"name":"Department of Clinical Pharmacology, St. Olav University Hospital, NO-7006 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joachim","family":"Frost","sequence":"first","affiliation":[{"name":"Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), NO-7491 Trondheim, Norway"},{"name":"Department of Clinical Pharmacology, St. Olav University Hospital, NO-7006 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,2,4]]},"reference":[{"key":"2020062302235374200_ref1","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1742-7843.2009.00517.x","article-title":"Active-site concentrations of chemicals - are they a better predictor of effect than plasma\/organ\/tissue concentrations?","volume":"106","author":"Hammarlund-Udenaes","year":"2010","journal-title":"Basic Clinical Pharmacology and Toxicology"},{"key":"2020062302235374200_ref2","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/0379-0738(90)90182-X","article-title":"Post-mortem drug redistribution \u2014 A toxicological nightmare","volume":"45","author":"Pounder","year":"1990","journal-title":"Forensic Science International"},{"key":"2020062302235374200_ref3","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.forsciint.2006.02.013","article-title":"The redistribution of selected psychiatric drugs in post-mortem cases","volume":"164","author":"Rodda","year":"2006","journal-title":"Forensic Science International"},{"key":"2020062302235374200_ref4","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.forsciint.2012.05.028","article-title":"The time-dependant post-mortem redistribution of antipsychotic drugs","volume":"222","author":"Saar","year":"2012","journal-title":"Forensic Science International"},{"key":"2020062302235374200_ref5","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":"2020062302235374200_ref6","doi-asserted-by":"crossref","first-page":"95","DOI":"10.18773\/austprescr.2015.032","article-title":"Concerns about quetiapine","volume":"38","author":"Brett","year":"2015","journal-title":"Australian prescriber"},{"key":"2020062302235374200_ref7","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1007\/s00228-017-2281-8","article-title":"The antipsychotic agent quetiapine is increasingly not used as such: Dispensed prescriptions in Norway 2004-2015","volume":"73","author":"Gjerden","year":"2017","journal-title":"European Journal of Clinical Pharmacology"},{"key":"2020062302235374200_ref8","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1097\/JCP.0000000000000338","article-title":"Off-label prescriptions of low-dose quetiapine and mirtazapine for insomnia in The Netherlands","volume":"35","author":"Kamphuis","year":"2015","journal-title":"Journal of Clinical Psychopharmacology"},{"key":"2020062302235374200_ref9","article-title":"Quetiapine versus other atypical antipsychotics for schizophrenia","author":"Komossa","year":"2010","journal-title":"The Cochrane Database of Systematic Reviews"},{"key":"2020062302235374200_ref10","doi-asserted-by":"crossref","first-page":"219","DOI":"10.2147\/nedt.2007.3.2.219","article-title":"Quetiapine in the treatment of schizophrenia and related disorders","volume":"3","author":"Riedel","year":"2007","journal-title":"Neuropsychiatric Disease and Treatment"},{"key":"2020062302235374200_ref11","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/FTD.0b013e31817fd5ed","article-title":"Pharmacokinetics and pharmacodynamics of quetiapine in a patient with a massive overdose","volume":"30","author":"Bodmer","year":"2008","journal-title":"Therapeutic Drug Monitoring"},{"key":"2020062302235374200_ref12","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/YIC.0000000000000124","article-title":"A thorough QT study to evaluate the QTc prolongation potential of two neuropsychiatric drugs, quetiapine and escitalopram, in healthy volunteers","volume":"31","author":"Kim","year":"2016","journal-title":"International Clinical Psychopharmacology"},{"key":"2020062302235374200_ref13","doi-asserted-by":"crossref","DOI":"10.1002\/14651858.CD007815.pub2","article-title":"Quetiapine versus typical antipsychotic medications for schizophrenia","author":"Suttajit","year":"2013","journal-title":"The Cochrane Database of Systematic Reviews"},{"key":"2020062302235374200_ref14","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1016\/S0140-6736(09)60742-X","article-title":"11-year follow-up of mortality in patients with schizophrenia: A population-based cohort study (FIN11 study)","volume":"374","author":"Tiihonen","year":"2009","journal-title":"Lancet"},{"key":"2020062302235374200_ref15","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1037\/1064-1297.5.3.216","article-title":"The expanding indications for clozapine","volume":"5","author":"Young","year":"1997","journal-title":"Experimental Clinical Psychopharmacology"},{"key":"2020062302235374200_ref16","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1097\/MJT.0000000000000715","article-title":"Clozapine Rechallenge after major adverse effects: Clinical guidelines based on 259 cases","volume":"25","author":"Manu","year":"2018","journal-title":"American Journal of Therapeutics"},{"key":"2020062302235374200_ref17","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1177\/1060028014550645","article-title":"Risk of QT\/QTc prolongation among newer non-SSRI antidepressants","volume":"48","author":"Jasiak","year":"2014","journal-title":"Annals of Pharmacotherapy"},{"key":"2020062302235374200_ref18","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1093\/jat\/bky018","article-title":"Distribution of eight QT-prolonging drugs and their main metabolites between Postmortem cardiac tissue and blood reveals potential pitfalls in toxicological interpretation","volume":"42","author":"Mikkelsen","year":"2018","journal-title":"Journal of Analytical Toxicology"},{"key":"2020062302235374200_ref19","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1097\/01.jcp.0000106229.36344.67","article-title":"Postmortem clozapine levels","volume":"24","author":"De Leon","year":"2004","journal-title":"Journal of Clinical Psychopharmacology"},{"key":"2020062302235374200_ref20","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1093\/jat\/bkv072","article-title":"Postmortem Quetiapine reference concentrations in brain and blood","volume":"39","author":"Skov","year":"2015","journal-title":"Journal of Analytical Toxicology"},{"key":"2020062302235374200_ref21","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jchromb.2012.12.039","article-title":"Quantitative determination of fifteen basic pharmaceuticals in ante- and post-mortem whole blood by high pH mobile phase reversed phase ultra high performance liquid chromatography-tandem mass spectrometry","volume":"927","author":"Amundsen","year":"2013","journal-title":"Journal of Chromatography B, Analytical Technologies in the Biomedical and Life Sciences"},{"key":"2020062302235374200_ref22","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/jat.2944","article-title":"Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases","volume":"34","author":"Lopez-Guarnido","year":"2014","journal-title":"Journal of Applied Toxicology"},{"key":"2020062302235374200_ref23","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":"2020062302235374200_ref24","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1093\/jat\/23.6.541","article-title":"Tissue distribution of mirtazapine (Remeron) in postmortem cases","volume":"23","author":"Moore","year":"1999","journal-title":"Journal of Analytical Toxicology"},{"key":"2020062302235374200_ref25","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1093\/jat\/30.4.287","article-title":"Tissue distribution of quetiapine in 20 cases in Virginia","volume":"30","author":"Flammia","year":"2006","journal-title":"Journal of Analytical Toxicology"},{"key":"2020062302235374200_ref26","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/jat\/bks054","article-title":"Simultaneous determination of 25 common pharmaceuticals in whole blood using ultra-performance liquid chromatography-tandem mass spectrometry","volume":"36","author":"Nielsen","year":"2012","journal-title":"Journal of Analytical Toxicology"},{"key":"2020062302235374200_ref27","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1255\/ejms.1338","article-title":"Drug detection and quantification directly from tissue using novel ionization methods for mass spectrometry","volume":"21","author":"Wang","year":"2015","journal-title":"European Journal of Mass Spectrometry"},{"key":"2020062302235374200_ref28","doi-asserted-by":"crossref","first-page":"3019","DOI":"10.1021\/ac020361s","article-title":"Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS\/MS","volume":"75","author":"Matuszewski","year":"2003","journal-title":"Analytical Chemistry"},{"key":"2020062302235374200_ref29","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.forsciint.2013.03.021","volume":"229","author":"Fisher","year":"2013","journal-title":"Forensic Science International"},{"key":"2020062302235374200_ref30","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1093\/jat\/bku080","article-title":"Long-term storage of authentic postmortem forensic blood samples at \u221220\u00b0C: Measured concentrations of benzodiazepines, central stimulants, opioids and certain medicinal drugs before and after storage for 16\u201318 years","volume":"38","author":"Karinen","year":"2014","journal-title":"Journal of Analytical Toxicology"},{"key":"2020062302235374200_ref31","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1111\/j.1556-4029.2006.00067.x","article-title":"The influence of site of collection on postmortem morphine concentrations in heroin overdose victims","volume":"51","author":"Crandall","year":"2006","journal-title":"Journal of Forensic Sciences"},{"key":"2020062302235374200_ref32","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"}],"container-title":["Journal of Analytical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/jat\/advance-article-pdf\/doi\/10.1093\/jat\/bkaa002\/33344573\/bkaa002.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jat\/article-pdf\/44\/5\/440\/33417839\/bkaa002.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/jat\/article-pdf\/44\/5\/440\/33417839\/bkaa002.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,2,24]],"date-time":"2021-02-24T22:37:59Z","timestamp":1614206279000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jat\/article\/44\/5\/440\/5722308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,2,4]]},"references-count":32,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,2,4]]},"published-print":{"date-parts":[[2020,4,2]]}},"URL":"https:\/\/doi.org\/10.1093\/jat\/bkaa002","relation":{},"ISSN":["0146-4760","1945-2403"],"issn-type":[{"value":"0146-4760","type":"print"},{"value":"1945-2403","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,4]]},"published":{"date-parts":[[2020,2,4]]}}}