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Nitrobenzodiazepines: Postmortem brain and blood reference concentrations.

Louise Skov1, Karen Marie Dollerup Holm1, Kristian Linnet1

  • 1Section of Forensic Chemistry, Department of Forensic Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Frederik V's Vej 11, DK-2100 Copenhagen Ø, Denmark.

Forensic Science International
|September 30, 2016
PubMed
Summary
This summary is machine-generated.

This study establishes reference concentrations for nitrobenzodiazepines in postmortem brain and blood. Brain tissue is a reliable alternative to femoral blood for toxicology, showing low pre-analytical variation.

Keywords:
Femoral bloodHuman brainNitrobenzodiazepinesPostmortem reference concentrationsPre-analytical variation

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Area of Science:

  • Forensic Toxicology
  • Neuroscience
  • Pharmacology

Background:

  • Postmortem toxicology relies on reference concentrations for accurate interpretation of results.
  • Femoral blood is the traditional specimen, but postmortem redistribution can complicate interpretation.
  • Brain tissue is proposed as a viable alternative due to potential redistribution issues in blood.

Purpose of the Study:

  • To determine reference concentrations for clonazepam, flunitrazepam, and nitrazepam in postmortem brain and femoral blood.
  • To investigate the utility of brain tissue as an alternative matrix for postmortem benzodiazepine analysis.
  • To compare drug and metabolite concentrations and ratios between brain and blood.

Main Methods:

  • Quantification of nitrobenzodiazepines and their 7-aminometabolites in postmortem brain and femoral blood samples.
  • Analysis performed using liquid chromatography-tandem mass spectrometry (LC-MS-MS).
  • Study included 69 cases, categorizing drug significance for death.

Main Results:

  • Reference concentrations for clonazepam, flunitrazepam, and nitrazepam were established in both matrices.
  • Brain-to-blood ratios for parent drugs (clonazepam, nitrazepam) were significantly higher (5.5, 4.7) than for metabolites (0.4-0.5).
  • A strong positive correlation (rs 0.77-0.96) was observed between brain and blood concentrations; brain showed low pre-analytical variation (5.9%).

Conclusions:

  • Postmortem brain tissue is a useful and reliable alternative to femoral blood for analyzing nitrobenzodiazepines.
  • Established reference concentrations aid in interpreting postmortem toxicology findings for these benzodiazepines.
  • The study provides valuable data for forensic investigations involving clonazepam, flunitrazepam, and nitrazepam.