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Postmortem tricyclic antidepressant concentrations: assessing cause of death using parent drug to metabolite ratio.

In 9 of 13 medical examiner cases in which death was caused by tricyclic antidepressant (TCA) overdose, the mean postmortem liver and blood concentrations were 200 micrograms/g and 4.0 micrograms/mL, respectively. In comparison, in 4 of 13 cases in which the causes of death were not TCA related but involved therapeutic doses of TCA, the mean liver and blood levels were 29.0 micrograms/g and 1.3 micrograms/mL, respectively. The parent drug to major metabolite ratio in liver was 6.3:1 in overdose cases and 0.5:1 in therapeutic cases. The ratio in blood was greater than 1.0 in both overdose and therapeutic ingestions. We concluded that liver TCA concentrations should be quantitated to specify manner of death. For cases in which the manner of death was ambiguous, the liver parent drug to major metabolite ratio aided in the decision process.