The distribution of opiates, cocaine and their metabolites in skeletal muscle tissue and vitreous humour as an aid to post-mortem toxicological interpretation

摘要

Post-mortem blood drug concentrations vary greatly and as a consequence of post-mortem change and redistribution may not reflect the concentration at the time of death. Tissues that are located away from central drug reservoirs and that lack esterase activity, e.g. muscle and vitreous humour (VH), have the potential to provide more reliable post-mortem toxicological specimens. In the absence of a blood sample the toxicologist may have to rely on such tissues yet few studies have been undertaken to examine the relationship between drugs in blood and less conventional tissues at the time of death. The purpose of this study was to investigate the distribution of opiates (heroin specific compounds) and cocaine and their respective metabolites in VH and muscle with a view to elucidating the interpretive value of these tissues. Analytical methods were developed and validated to measure drug concentrations in blood, VH and muscle, including throughout the rectus femoris thigh muscle, in cases of drug related death. To assist with interpretation of drug concentrations measured in post-mortem tissues the in vitro stability of cocaine and 6-acetylmorphine (6AM) was examined during the putrefactive process and under different storage conditions. Relationships between blood and tissue drug concentrations were assessed in relation to case circumstances with particular focus on the approximation of survival time. In contrast to a report previously published in the literature, this study found the concentration of cocaine, and its metabolites, benzoylecgonine (BZE) and cocaethylene (COET), to be uniformly distributed throughout the thigh muscle (n = 7). Concentrations of cocaine in muscle were markedly higher than in blood and correlated well with the blood. The stability of cocaine in muscle tissue was found to greatly exceed that in blood and VH. These preliminary results also indicated that the cocaine to BZE ratio measured in both muscle and VH may be of value in the assessment of survival time. These findings promote the use of muscle as a toxicological specimen for cocaine determinations. Further work is required to validate these findings and to examine the distribution of opiates in muscle, which could not be assessed in this study. The relationship between femoral blood and vitreous humour morphine concentration (n = 70) was found to be dependent on survival time and possibly influenced by accumulation of morphine in the VH. These findings demonstrate that the concentration of morphine in blood cannot be inferred from that measured in the VH. The VH provided a useful adjunct to interpretation owing to the prolonged detection of 6AM in this matrix. The addition of 1.5% sodium fluoride to VH was found to be essential for 6AM stability during storage. The utility of rapidly metabolised heroin specific compounds in blood as indicators of survival period following heroin intake and the role of concomitant drug consumption in heroin fatalities was also discussed in this thesis.