The forensic toxicology of antipsychotic drugs: method development, stability and redistribution studies

Antipsychotic drugs are commonly prescribed for the treatment of a number of metal illnesses. However, people suffering from mental illness are at a higher risk of suicide than healthy individuals and these drugs are associated with the onset and exacerbation of particular comorbidities. Accordingly, antipsychotic drugs are commonly detected in cases reported to the coroner. The detection and quantification of antipsychotic drugs in postmortem specimens and the ensuing interpretation of these results therefore play an important role determining the cause of death. A study is presented which describes the development of a comprehensive detection method for the analysis of antipsychotic drugs in whole blood, as well as research into several factors that can potentially alter blood concentrations after death, with a focus on post-mortem redistribution and stability of blood samples containing antipsychotic drugs. The research indicated that several antipsychotic drugs are prone to significant losses if stored at temperatures above 0 ºC, potentially compromising post-mortem drug results. Furthermore, the atypical antipsychotic drug olanzapine showed significant losses even if stored at temperatures below 0 ºC. Further analysis of the degradation of this commonly prescribed drug revealed 2-hydroxymethyl olanzapine as a new degradation product of olanzapine in aqueous solutions. The investigation of the post-mortem redistribution of antipsychotic drugs in peripheral blood specimens revealed that the majority of targeted drugs underwent a time-dependent bi-phasic process with an initial increase followed by a decrease in concentration. However, different patterns of change were also present. The results highlighted the need for immediate sample collection post-admission of a deceased person to the mortuary, in addition to appropriate sample storage; pre- and post-analysis. When interpreting post-mortem blood results of antipsychotic drugs, the factors described in this thesis must be considered as sources of potential variation.