Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h

Peter D. Maskell, Mohammed Albeishy, Giorgia De Paoli, Nathan E. Wilson, L. Nitin Seetohul

Research output: Contribution to journalArticle

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Abstract

The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised. Following death rabbits were placed in a supine position at room temperature and divided into three groups namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h after death. Various samples which included femoral blood, cardiac blood, lung, liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone marrow and skeletal muscle were taken. The samples were analysed with a validated LC-MS/MS method. It was observed that within minutes there was a significant increase in free morphine postmortem femoral blood concentration compared to the antemortem sample (0.01 ± 0.01 to 0.05 ± 0.02 mg/L).Various other changes in free morphine and metabolite concentrations were observed during the course of the experiment in various tissues. Principal component analysis was used to investigate possible correlations between free morphine in the various samples. Some correlations were observed but gave poor predictions (>20 % error) when back calculating. The results suggest that rabbits are a good model for further studies of postmortem redistribution but that further study and understanding of the phenomena is required before accurate predictions of the blood concentration at the time of death are possible.

Original languageEnglish
Pages (from-to)519-531
Number of pages13
JournalInternational Journal of Legal Medicine
Volume130
Issue number2
Early online date12 Apr 2015
DOIs
Publication statusPublished - Mar 2016

Fingerprint

Heroin
Morphine
Rabbits
Autopsy
Thigh
Pharmaceutical Preparations
Abdominal Subcutaneous Fat
Vitreous Body
Liver
Supine Position
Principal Component Analysis
morphine-3-glucuronide
Veins
Skeletal Muscle
Bone Marrow
Kidney
Lung
Temperature

Cite this

Maskell, Peter D. ; Albeishy, Mohammed ; De Paoli, Giorgia ; Wilson, Nathan E. ; Seetohul, L. Nitin. / Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h. In: International Journal of Legal Medicine. 2016 ; Vol. 130, No. 2. pp. 519-531.
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abstract = "The interpretation of postmortem drug levels is complicated by changes in drug blood levels in the postmortem period, a phenomena known as postmortem drug redistribution. We investigated the postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in a rabbit model. Heroin (1 mg/kg) was injected into anesthetised rabbit; after 1 h, an auricular vein blood sample was taken and the rabbit was euthanised. Following death rabbits were placed in a supine position at room temperature and divided into three groups namely (1) immediate autopsy, (2) autopsy after 30 minutes and (3) autopsy 24 h after death. Various samples which included femoral blood, cardiac blood, lung, liver, kidney, vitreous humour, subcutaneous and abdominal fat, liver, bone marrow and skeletal muscle were taken. The samples were analysed with a validated LC-MS/MS method. It was observed that within minutes there was a significant increase in free morphine postmortem femoral blood concentration compared to the antemortem sample (0.01 ± 0.01 to 0.05 ± 0.02 mg/L).Various other changes in free morphine and metabolite concentrations were observed during the course of the experiment in various tissues. Principal component analysis was used to investigate possible correlations between free morphine in the various samples. Some correlations were observed but gave poor predictions (>20 {\%} error) when back calculating. The results suggest that rabbits are a good model for further studies of postmortem redistribution but that further study and understanding of the phenomena is required before accurate predictions of the blood concentration at the time of death are possible.",
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Postmortem redistribution of the heroin metabolites morphine and morphine-3-glucuronide in rabbits over 24 h. / Maskell, Peter D.; Albeishy, Mohammed; De Paoli, Giorgia; Wilson, Nathan E.; Seetohul, L. Nitin.

In: International Journal of Legal Medicine, Vol. 130, No. 2, 03.2016, p. 519-531.

Research output: Contribution to journalArticle

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