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Time- and Site-dependent postmortem redistribution of antidepressants and neuroleptics in blood and alternative matrices


Brockbals, Lana; Staeheli, Sandra N; Gascho, Dominic; Ebert, Lars C; Kraemer, Thomas; Steuer, Andrea Eva (2020). Time- and Site-dependent postmortem redistribution of antidepressants and neuroleptics in blood and alternative matrices. Journal of analytical toxicology:Epub ahead of print.

Abstract

Postmortem redistribution (PMR) leads to challenges in postmortem case interpretation. Particularly antidepressants and neuroleptics are expected to undergo PMR based on their physico-chemical properties. For the current study, time- and site-dependent PMR of 20 antidepressants and neuroleptics were investigated in humans (authentic cases); five of which are discussed in detail (citalopram, mirtazapine, quetiapine, risperidone and venlafaxine) along with two metabolites (9-OH-risperidone and O-desmethylvenlafaxine). Blood [femoral (pB) and heart blood (HB)] and tissue biopsy samples (lung, kidney, liver, spleen, thigh muscle and adipose tissue) were collected upon admission to the institute utilizing a computed tomography-guided sample collection workflow (t1). Approximately 24 h later (t2; mean 23 ± 9.3 h), samples from the same body regions were collected manually. Liquid chromatography–tandem mass spectrometry was used for quantification. Most antidepressants and neuroleptics showed significant time-dependent concentration changes indicating the occurrence of PMR. For the first time, two phases of redistribution in pB for quetiapine were proposed (concentration decreases in the early postmortem phase, followed by concentration increases) and contrasting existing literature, both concentration increases and decreases in pB overtime were observed for risperidone and 9-OH-risperidone. Venlafaxine and its metabolite only showed minimal concentration changes, while citalopram exhibited a trend for concentration increases and mirtazapine for concentration decreases in pB overtime. Based on time-dependent tissue data, passive diffusion processes along the muscle-to-pB, liver-to-HB and lung-to-HB concentration gradients could be proposed along with bacterial degradation. Overall, no case interpretation had to be adjusted, which suggests that PMR changes of antidepressants and neuroleptics do not seem to be relevant for forensic case interpretation within the 24 h period that was investigated. However, limitations of the current study (e.g., temperature-controlled storage of the bodies) could have led to an underestimation of occurring postmortem changes, hence, interpretation of postmortem results should always be conducted with care, considering PMR phenomena and inter-individual variability.

Abstract

Postmortem redistribution (PMR) leads to challenges in postmortem case interpretation. Particularly antidepressants and neuroleptics are expected to undergo PMR based on their physico-chemical properties. For the current study, time- and site-dependent PMR of 20 antidepressants and neuroleptics were investigated in humans (authentic cases); five of which are discussed in detail (citalopram, mirtazapine, quetiapine, risperidone and venlafaxine) along with two metabolites (9-OH-risperidone and O-desmethylvenlafaxine). Blood [femoral (pB) and heart blood (HB)] and tissue biopsy samples (lung, kidney, liver, spleen, thigh muscle and adipose tissue) were collected upon admission to the institute utilizing a computed tomography-guided sample collection workflow (t1). Approximately 24 h later (t2; mean 23 ± 9.3 h), samples from the same body regions were collected manually. Liquid chromatography–tandem mass spectrometry was used for quantification. Most antidepressants and neuroleptics showed significant time-dependent concentration changes indicating the occurrence of PMR. For the first time, two phases of redistribution in pB for quetiapine were proposed (concentration decreases in the early postmortem phase, followed by concentration increases) and contrasting existing literature, both concentration increases and decreases in pB overtime were observed for risperidone and 9-OH-risperidone. Venlafaxine and its metabolite only showed minimal concentration changes, while citalopram exhibited a trend for concentration increases and mirtazapine for concentration decreases in pB overtime. Based on time-dependent tissue data, passive diffusion processes along the muscle-to-pB, liver-to-HB and lung-to-HB concentration gradients could be proposed along with bacterial degradation. Overall, no case interpretation had to be adjusted, which suggests that PMR changes of antidepressants and neuroleptics do not seem to be relevant for forensic case interpretation within the 24 h period that was investigated. However, limitations of the current study (e.g., temperature-controlled storage of the bodies) could have led to an underestimation of occurring postmortem changes, hence, interpretation of postmortem results should always be conducted with care, considering PMR phenomena and inter-individual variability.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Legal Medicine
Dewey Decimal Classification:340 Law
610 Medicine & health
510 Mathematics
Uncontrolled Keywords:Toxicology, Analytical Chemistry, Health, Toxicology and Mutagenesis, Chemical Health and Safety, Environmental Chemistry
Language:English
Date:28 August 2020
Deposited On:03 Sep 2020 07:27
Last Modified:03 Sep 2020 07:27
Publisher:Preston Publications
ISSN:0146-4760
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1093/jat/bkaa092
PubMed ID:32856054
Project Information:
  • : FunderSNSF
  • : Grant ID310030_165875
  • : Project TitleSystematic Studies on Postmortem Toxicology

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