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Monday, August 25 Postmortem Analysis and Drug Stability

Gerostamoulos J., Drummer O.H.
Victorian Institute of Forensic Medicine and Department of Forensic Medicine, Monash University,57-83 Kavanagh Street, Southbank, Melbourne, Victoria, 3006, Australia

The lack of information regarding the distribution of morphine and its conjugate metabolites in postmortem tissues was addressed in an attempt to better understand the contribution of these compounds to the toxicity of heroin and/or morphine. The distribution of morphine and its principal metabolites was determined in a variety of specimens obtained from 40 individuals who had died as a result of heroin use. The concentrations of these morphine species were also correlated in various tissues.

The average concentration of morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), free morphine (FM) and total morphine (TM) in femoral blood were 0.61 mg/L, 0.13 mg/L, 0.31 mg/L and 0.78 mg/L, respectively. The highest concentrations of M3G and M6G were found in urine, kidney and liver. Concentrations of M6G were on average 1/5 that of M3G and, with the exception of urine, concentrations of M6G were smaller than that of free morphine. Smaller amounts of M3G/M6G were detected in CSF and vitreous humour, and no glucuronides were detected in brain tissue. Glucuronide concentrations in femoral blood showed good correlations with concentrations in plasma, vitreous humour and liver but not in CSF, kidney and urine. The absence of glucuronides in brain tissue (cerebellum) and the corresponding low concentrations of glucuronides in CSF would suggest that glucuronides do not cross the blood brain barrier easily. Nor do they appear to be formed to any great degree in brain. The presence of morphine species inCSF could well be due to diffusion from blood, rather than production in brain. However the presence and/or production of glucuronides in other regions of the brain cannot be excluded. The greater potency and longer half life of M6G, suggest that even at low concentrations of M6G, this metabolite can contribute significantly to the effect of morphine in a heroin user. Concentrations of M3G, M6G and TM were similar in plasma and blood suggesting that either fluid can be used in postmortem analysis.

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