Post mortem tissue distribution of quetiapine in forensic autopsies

• Published in: Forensic science international Vol. 315; p. 110413
• Main Authors: Breivik, Håvard, Frost, Joachim, Løkken, Trine N., Slørdal, Lars
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.10.2020; Elsevier Limited
• Subjects: Accreditation; Adult; Aged; Anesthesia; Antipsychotic; Antipsychotic Agents - analysis; Antipsychotic Agents - pharmacokinetics; Antipsychotics; Autopsies; Autopsy; Blood; Blood levels; Brain; Brain Chemistry; Brain research; Cases (containers); death; Drug dosages; drug toxicity; Ecstasy; Fatalities; Female; Femur; Forensic; Forensic science; Forensic sciences; Forensic Toxicology; heart; Homogenization; Humans; Intoxication; Laboratories; Libraries; Liquid chromatography; Liquid-liquid extraction; Liver; Liver - chemistry; Male; Mass spectrometry; Methods; Middle Aged; Morphine; mortality; Muscle; Muscle, Skeletal - chemistry; Muscles; necropsy; Plasma; poisoning; Post mortem redistribution; Postmortem Changes; Psychotropic drugs; Quetiapine; Quetiapine Fumarate - analysis; Quetiapine Fumarate - pharmacokinetics; Ratios; Skeletal muscle; Substance-Related Disorders - mortality; Tissue; tissue distribution; Tissues; Toxicity; Toxicology; Young Adult; Norway; Brain; Tissue; Toxicology; Liver; Antipsychotic; Forensic; Muscle; Liquid chromatography; Post mortem redistribution; Mass spectrometry; Quetiapine; Blood
• ISSN: 0379-0738; 1872-6283; 1872-6283
• DOI: 10.1016/j.forsciint.2020.110413

•A novel LC-MSMS method for quantification of quetiapine in solid tissues was applied.•Quetiapine is subject to post mortem redistribution.•Quetiapine concentration levels tend to be considerably higher in liver tissue than in blood, muscle or brain tissue post mortem.•Post mortem quetiapine concentration levels in skeletal muscle are generally similar to concentration levels in femoral blood.•Inter-case variability of quetiapine concentration level ratios between matrices was extensive. The antipsychotic drug quetiapine is widely used, and increasingly prescribed off-label. Furthermore, quetiapine use has been linked to increased mortality rates, most likely due to a range of cardiovascular and metabolic adverse effects. This makes quetiapine a relevant substance in forensic toxicology casework. Quetiapine is believed to undergo significant post mortem redistribution. Herein, we present tissue distribution and concentration levels of quetiapine in post mortem whole blood, brain tissue, skeletal muscle, and liver tissue in a series of 14 quetiapine-implicated forensic autopsy cases along with the quetiapine concentrations determined in femoral whole blood in conjunction with the autopsies. Quantification was performed using liquid-liquid extraction and a validated UPLC-MSMS method. Six deaths were attributed to intoxication with quetiapine in combination with other substances; there were no quetiapine monointoxications. In eight cases, death was attributed to other causes than drug toxicity. In a majority of the cases, liver tissue contained the highest quetiapine concentrations, while whole blood levels were the lowest. Central (heart) blood concentrations were generally higher than peripheral (femoral) blood levels. Quetiapine concentrations in femoral blood correlated most strongly with concentrations in skeletal muscle. Otherwise, there was no consistent hierarchy of quetiapine tissue concentrations, and the tissue distribution showed no clear relationship with the length of the post mortem interval.