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This dissertation describes a series of toxicological studies carried out in order to better understand the role of monoamine-active drugs in drug- related deaths. A simple, robust method for determining psychiatric drugs and metabolites was devised using positive mode APESI LC-MS at basic pH. This method was modified to enable determination of multiple commonly abused drugs. It was discovered that both psychiatric drugs and drugs of abuse could be detected using similar chromatographic parameters. Target drug and metabolite concentrations were determined in postmortem tissue specimens. Drug concentrations were highest in bile and liver and lowest in vitreous humour. Four patterns of distribution were observed, with extent of biliary excretion corresponding to molecular weights. Concentrations in other tissues were compared to those in blood. Several significant correlations were observed, suggesting target drug concentrations in blood could be predicted using these tissues, or could be analysed in lieu of blood in cases of extensive exsanguination or putrefaction. Antipsychotic concentrations were determined in various brain regions from schizophrenics to determine whether such drugs partition preferentially into particular regions. A further aim was to investigate whether trends exist in how they distribute in brain as a drug class. It was found that if regional drug concentrations were normalised for those in cerebellum, they distributed into three distinct patterns, corresponding to structural features of different phenothiazines. Drug concentrations in certain regions were significantly correlated with selected drug properties, providing the ability to predict their partitioning into such regions. Significant correlations were observed between drug concentrations in selected brain regions and those in blood, suggesting concentrations in these brain regions can be used to predict those in blood, and vice-versa.