ABSTRACTS AND CV´s LECTURERS / CHAIRPERSONS Dimitri Gerostamoulos Victorian Institute of Forensic Medicine, Department of Forensic Medicine, Monash University, Melbourne, Australia POSTMORTEM DRUG CHANGES AND REDISTRIBUTION – HOW TO INTERPRET FORENSIC TOXICOLOGY RESULTS There are many changes that occur postmortem following the death of an individual. These changes can affect the way that any drug results are interpreted, especially for medico-legal casework. Forensic toxicologists have for a long time acknowledged that many processes such as postmortem redistribution (PMR), drug instability and metabolic changes can significantly affect the interpretation of toxicology. PMR is an accepted toxicological phenomenon which may affect the interpretation of post-mortem (PM) blood concentrations. The extent of PMR is not well understood, nor described for most drugs. Recently studies have shown that changes can occur over time irrespective of the sample type. The PMR of selected drugs from102 cases comparing blood specimens taken at admission of the deceased to the mortuary to blood specimens taken at autopsy showed that more than 45% of all drugs increased in concentration by at least 10% or more. Indeed some drugs such as venlafaxine, mirtazapine and paroxetine showed an average increase of ~30%, irrespective of the length of the post-mortem interval [1]. This work showed that caution must be exercised when forming toxicological opinions from concentrations determined solely from autopsy specimens. While femoral blood is thought to reduce PMR, this study showed that for some drugs significant redistribution can occur even when taking peripheral specimens irrespective of the delay in the postmortem interval. In addition to PMR, drug changes or the instability of some drugs must be considered as drugs change or are converted to metabolites or other by-products in the postmortem interval. Drugs such as cocaine, heroin, nitro-benzodiazepines [2] and olanzapine [3] are all converted to their respective metabolites quickly following death. In some instances drugs are entirely converted to undetectable metabolites or concentrations which can therefore limit the interpretation of toxicology results. Post-mortem artifacts may also change the ratios of metabolites to parent drug in blood. This may be important in some instances where ratios of unconjugated to conjugated drug can assist in indicating whether death occurred within a short time of administration of the drug into the body. The metabolic predisposition of individuals to metabolise drugs in varying capacities also creates issues for the toxicologists when determining the significance of drug concentrations at postmortem. High concentrations of drugs which can lead to toxic life-threatening situations can be due to metabolic inhibition of some enzymic processes rather than an ingested overdose. Drugs at seemingly therapeutic concentrations can also lead to adverse effects when contraindicated (eg serotonin syndrome). 1 ABSTRACTS AND CV´s LECTURERS / CHAIRPERSONS Drug concentrations may also change due to a number of processes including trauma, putrefaction, immersion in water, etc. and there is much that remains unknown in terms of being able to interpret toxicology results with certainty. Hence it is essential that forensic toxicologists are aware that such phenomena exist and that the process of interpreting post-mortem toxicology results is not straightforward. Interpretation should be considered only after all the elements in an investigation have been collated including, but not limited to, autopsy findings, histopathology, the contribution of natural disease, the known circumstances of the case and the medical history of the deceased. References 1. Gerostamoulos, D., et al., The effect of the postmortem interval on the redistribution of drugs: a comparison of mortuary admission and autopsy blood specimens. Forensic Sci Med Pathol, 2012. 8(4): p. 373-9. 2. Robertson, M.D. and O.H. Drummer, High-performance liquid chromatographic procedure for the measurement of nitrobenzodiazepines and their 7-amino metabolites in blood. J Chromatogr B Biomed Appl, 1995. 667(1): p. 179-84. 3. Saar, E., et al., Identification of 2-hydroxymethyl-olanzapine as a novel degradation product of olanzapine. Forensic Sci Int, 2012. 220(1-3): p. 74-9. Dr. Dimitri Gerostamoulos is currently Chief Toxicologist at the Victorian Institute of Forensic Medicine, Coronial Services Centre, 65 Kavanagh Street, Southbank, Victoria 3006. He is a Toxicologist and Pharmacologist, and holds a Degree of Doctor of Philosophy (Medicine) in the field of Forensic Toxicology and a Bachelor of Science (Honours) Degree, both from Monash University. He is an approved analyst under Section 57B of the Road Safety Act of Victoria and has published numerous scientific papers and chapters in books and is an active member of The International Association of Forensic Toxicologists (TIAFT). He is also a member the Society of Forensic Toxicologists (SOFT) and the Forensic and clinical Toxicology Association of Australasia (FACTA Inc). Dr Gerostamoulos is also an approved assessor for the National Association of Testing Authorities, Australia (NATA) in Forensic Science. Dr Gerostamoulos has given evidence in over 110 cases in Supreme court, County court, Committal proceedings at Magistrates Court and at Coronial Inquests in the field of forensic toxicology and pharmacology and have provided opinions on a number of other cases around Australia in relation to the pharmacology of drugs, effects of drugs in drivers, and analytical and toxicological issues. 2