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Elucidating the potential role of microorganisms in postmortem biotransformation: a comparison of clonazolam and its

Brittany K Casey1, Donna M Papsun1, Anna Mudd2

  • 1NMS Laboratories, Horsham, PA 19044, United States.

Journal of Analytical Toxicology
|August 5, 2024
PubMed

Insights

Postmortem microbial biotransformation of clonazolam is uncommon, with parent drug and metabolite detection differing significantly between postmortem and drug-impaired driving cases. This study investigates clonazolam

Area of Science:

  • Forensic Toxicology
  • Pharmacology
  • Microbiology

Background:

  • Clonazolam, a potent designer triazolobenzodiazepine, is known for anxiolytic and sedative effects and has been misused since 2012.
  • Previous studies indicate that gut bacteria can biotransform nitrobenzodiazepines during postmortem decomposition, affecting drug and metabolite concentrations.
  • Clonazolam possesses a nitro functional group, suggesting potential for similar microbial biotransformation, though specific studies are lacking.

Purpose of the Study:

  • To investigate the potential for postmortem (PM) microbial biotransformation of clonazolam.
  • To compare the occurrence and concentrations of clonazolam and its metabolite, 8-aminoclonazolam, in postmortem and driving under the influence of drugs (DUID) cases.

Main Methods:

  • Analysis of 288 PM cases and 54 DUID cases positive for 8-aminoclonazolam, reported between 2020 and 2023.
  • Quantification of clonazolam and 8-aminoclonazolam concentrations in biological samples.
  • Comparison of the concurrent identification rates of parent drug and metabolite between PM and DUID case groups.

Main Results:

  • Concurrent detection of clonazolam and 8-aminoclonazolam was significantly less frequent in PM cases (0.30%) compared to DUID cases (38%).
  • Median concentrations of 8-aminoclonazolam were higher in PM cases (13 ng/mL) than in DUID cases (19 ng/mL).
  • Clonazolam concentrations varied, with a single PM case at 13 ng/mL and a median of 4.0 ng/mL in DUID cases.

Conclusions:

  • Postmortem microbial biotransformation of clonazolam appears to be a less common phenomenon compared to other nitrobenzodiazepines.
  • The study provides valuable data in the absence of in vitro studies, offering an alternative method to investigate nitrobenzodiazepine biotransformation.
  • Differences in parent drug and metabolite detection highlight the importance of considering postmortem changes in forensic toxicology.

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