Disposition of morphine and codeine in blood and in brain samples in cases of fatal heroin overdose

When fatal heroin overdose is suspected, blood samples are traditionally analyzed by GC/MS, after extraction and derivatization, to determine the active metabolites 6-MAM and morphine. This method allows also to perform a so known “generic investigation” of the basic compounds, including impurities and cutting agents of “street heroin”, such as acetylcodeine and its metabolite codeine. The concentration of morphine in blood is usually the most important analytical result for the interpretation of the cause of death [1]. However, a number of overdose fatalities show relatively low blood concentrations of morphine, i.e. below or similar to those of living consumers or intoxicated heroin users [2]. This could be due to a variety of reasons, such as the relationship between lethal dose and current individual tolerance [3], the complexity of heroin metabolism, the presence of systemic dysfunction and the contemporary use of other drugs of abuse. Moreover, post-mortem redistribution or drug instability can affect the concentration of drugs in blood [4]. In post-mortem forensic toxicology the analysis of brain specimens may be also useful. Indeed, the sites of action of heroin and its main metabolites are primarily located in the central nervous system, so that concentrations in post-mortem brain samples are close or equal to those responsible for the toxic effects which caused death. Brain distribution pattern of “street” heroin metabolites (morphine and codeine) was investigated in two fatalities due to “acute narcotism” [5]. A suitable sample pretreatment prior to solid-phase-extraction was developed to achieve a good recovery of the analytes and to eliminate interfering species. After derivatization with MSTFA, samples were analyzed by GC/MS. Specificity, accuracy, precision and linearity of the method were evaluated. This method was applied to the analysis of six brain areas (hippocampus, frontal lobe, occipital lobe, nuclei, bulb and pons) coming from the two cases of heroin-related deaths. No evidence of accumulation of metabolites in a specific brain region was found, so bulb, which is the specimen that is usually taken during an autopsy, can be considered as representative of the drug concentration in the whole brain. Subsequently, the concentration of morphine and codeine in brain was investigated in fourteen samples belonging to cases of suspected fatal heroin overdose. Results were compared to those coming from the analysis of blood specimens. No correlation was found between the concentrations of morphine and codeine in blood and brain, but a higher ratio between codeine and morphine was found in brain, suggesting an accumulation and/or a slower metabolism of this more hydrophobic derivative in that compartment.