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An Investigation into the Distribution and Concentration of Drugs of Abuse within Different Body Compartments and Relationship with Toxicity

By Salah Ali Menshawi

Abstract

Pages 199-201 of Appendix I have been removed from the electronic version of this thesis due to copyright restrictions. The full version can be consulted at the University of Leicester Library.Femoral blood is preferable in post-mortem toxicological analysis but may not always be available. Alternative specimens such as cardiac blood, vitreous humour, stomach contents, bile, urine, hair, bone, liver and muscle may be used. However, only limited data are available for the interpretation of drug concentrations in these alternative specimens. The aim of the study was to investigate the distribution of drugs in different body compartments in relation to levels in femoral blood and their toxicity. All post-mortem specimens from 95 subjects were provided by Professor M Tsokos, Institute of Legal Medicine, Germany. Ethanol was measured by gas chromatography, whilst other drugs of abuse were initially screened for by immunoassays (in blood, hair and bone by Cozart drug immunoassay kit; urine by cloned enzyme donor immunoassay). A general drug screen and confirmation was performed on all specimens using gas chromatography/mass spectrometry and drug quantification was by high-pressure liquid chromatography-tandem mass spectrometry. Drug levels in femoral blood and median concentration ratios in relation to femoral blood (range) were as follows: ethanol 4-365mg/dL, median ratios for cardiac blood 1.9 (0.8:1-42.3:1), vitreous humour 1.6 (0.7:1-9.4:1), urine 6.5 (1.7:1-153:1) and bile 11.3 (1.0:1-34:1); for cocaine 5-2413ng/ml, median ratios for cardiac blood 1.2 (0.2:1-7.0:1), vitreous humour 1.4 (1.0:1-3.3:1), urine 4.9 (0.4:1->1000:1) and bile 7.0 (0.6:1-41.6:1); for methadone 7-1795 ng/ml, median ratios for cardiac blood 1.4 (0.6:1->3.9:1), vitreous humour 0.7 (0.04:1-0.99:1), urine 0.7 (0.3:1->3.9:1) and bile 2.9 (0.7:1->9.6:1); for morphine 7-1756 ng/ml, median ratios for cardiac blood 2.0 (0.9:1-11.5:1), vitreous humour 1.0 (0.4:1-18.5:1), urine 2.2 (0.1:1-56:1) and bile 24 (1.3:1 -> 195:1). Similarly, in liver and muscle for cocaine the median concentration ratio in ml/g was 0.2 (0.04:1-1.0:1) and 0.1 (0.1:1-2.5:1) respectively; for methadone 0.3 (0.2:1-<0.7:1) and 0.1 (0.05:1->0.7:1) respectively; and for morphine 0.6 (0.1:1-1.6:1) and 0.3 (0.1:1-1.6:1) respectively. In the majority of cases there was a good correlation between femoral blood levels and the concentration in other body compartments. This study has added to our knowledge and understanding of the usefulness of using alternative post-mortem specimens to study the distribution of drugs of abuse in different body compartments and how the concentrations relate to femoral blood levels and toxicity

Publisher: University of Leicester
Year: 2010
OAI identifier: oai:lra.le.ac.uk:2381/8572

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