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Postmortem metabolomics: strategies to assess time-dependent postmortem changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram

Brockbals, Lana; Wartmann, Yannick; Mantinieks, Dylan; Glowacki, Linda L; Gerostamoulos, Dimitri; Kraemer, Thomas; Steuer, Andrea E (2021). Postmortem metabolomics: strategies to assess time-dependent postmortem changes of Diazepam, Nordiazepam, Morphine, Codeine, Mirtazapine and Citalopram. Metabolites, 11(9):643.

Abstract

Postmortem redistribution (PMR) can result in artificial drug concentration changes following death and complicate forensic case interpretation. Currently, no accurate methods for PMR prediction exist. Hence, alternative strategies were developed investigating the time-dependent postmortem behavior of diazepam, nordiazepam, morphine, codeine, mirtazapine and citalopram. For 477 authentic postmortem cases, femoral blood samples were collected at two postmortem time-points. All samples were quantified for drugs of abuse (targeted; liquid chromatography-tandem mass spectrometry LC-MS/MS) and characterized for small endogenous molecules (untargeted; gas chromatography-high resolution MS (GC-HRMS). Trends for significant time-dependent concentration decreases (diazepam (n = 137), nordiazepam (n = 126)), increases (mirtazapine (n = 55), citalopram (n = 50)) or minimal median postmortem changes (morphine (n = 122), codeine (n = 92)) could be observed. Robust mathematical mixed effect models were created for the generalized postmortem behavior of diazepam and nordiazepam, which could be used to back-calculate drug concentrations towards a time-point closer to the estimated time of death (caution: inter-individual variability). Significant correlations between time-dependent concentration changes of morphine, mirtazapine and citalopram with individual endogenous molecules could be determined; no correlation was deemed strong enough for successful a posteriori estimation on the occurrence of PMR for specific cases. The current dataset did successfully lead to a significant knowledge gain in further understanding the time-dependent postmortem behavior of the studied drugs (of abuse).

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
Scopus Subject Areas:Health Sciences > Endocrinology, Diabetes and Metabolism
Life Sciences > Biochemistry
Life Sciences > Molecular Biology
Uncontrolled Keywords:Molecular Biology, Biochemistry, Endocrinology, Diabetes and Metabolism
Language:English
Date:20 September 2021
Deposited On:20 Dec 2021 13:22
Last Modified:26 Dec 2024 02:39
Publisher:MDPI Publishing
ISSN:2218-1989
OA Status:Gold
Free access at:PubMed ID. An embargo period may apply.
Publisher DOI:https://doi.org/10.3390/metabo11090643
PubMed ID:34564459
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  • Language: English
  • Licence: Creative Commons: Attribution 4.0 International (CC BY 4.0)

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