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Published on: September 1, 2016
Postmortem redistribution of morphine in rats
Abstract:
Because morphine is often found in the postmortem (PM) blood samples of patients treated with or abusing the drug, its causation in death has to be considered. The possibility of PM redistribution of the opioid drug has not been studied previously. We treated adult Wistar rats with 4 mg/kg of morphine i.m. and measured cardiac cavity levels at the time of death, by killing (2 h postdose) 24 and 96 h PM. Morphine concentrations rose from 41.4 +/- 13.2 ng/ml at death to 111.9 +/- 66.6 ng/ml at 24 h (p = 0.00036), with no additional increase at 96 h (98.7 +/- 21.7 ng/ml). After death there was accumulation of endogenous substances cross-reacting with the morphine radioimmunoassay. Although these attribute only 3% to total accumulation of morphine, they may complicate interpretation of morphine "readings" in patients who had not received the drug. Our study suggests that after death there is substantial redistribution of morphine. Elevated PM levels cannot necessarily by interpreted as representing antemortem concentrations.
Insights
Postmortem (PM) morphine levels in blood can increase significantly after death due to redistribution. These elevated concentrations may not reflect antemortem morphine levels, complicating death investigations.
Area of Science:
- Forensic Toxicology
- Pharmacology
- Postmortem Medicine
Background:
- Morphine is frequently detected in postmortem blood samples.
- Determining if morphine levels indicate cause of death is crucial.
- Postmortem redistribution of morphine has not been previously investigated.
Purpose of the Study:
- To investigate the phenomenon of postmortem morphine redistribution.
- To determine if postmortem morphine concentrations differ from antemortem levels.
- To assess the impact of postmortem redistribution on interpreting morphine levels in forensic cases.
Main Methods:
- Adult Wistar rats were administered morphine (4 mg/kg, intramuscular).
- Cardiac blood samples were collected at the time of death (2 hours postdose).
- Morphine concentrations were measured at 24 and 96 hours postmortem.
Main Results:
- Morphine concentrations in cardiac blood significantly increased from 41.4 ng/ml at death to 111.9 ng/ml at 24 hours postmortem (p = 0.00036).
- No significant additional increase was observed at 96 hours postmortem (98.7 ng/ml).
- Endogenous substances cross-reacting with the morphine assay were found, contributing minimally (3%) to the total accumulation.
Conclusions:
- Substantial redistribution of morphine occurs after death.
- Elevated postmortem morphine levels do not necessarily represent antemortem concentrations.
- Interpretation of postmortem morphine findings requires consideration of redistribution effects.
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