Brain concentrations and brain-blood ratios of amitriptyline and nortriptyline in forensic postmortem cases

Concentrations of amitriptyline and nortriptyline in postmortem blood samples may not accurately reflect the concentrations at the time of death due to postmortem redistribution or degradation. The brain is suggested as an alternative matrix since it is less subjected to postmortem redistribution and more protected against trauma and putrefaction, but reference concentrations in brain tissue are scarce. In this study, we aimed to provide concentrations in brain tissue and brain-blood ratios in 53 postmortem cases, where amitriptyline and/or nortriptyline were detected. To establish reference levels, each case was assigned to one of three classes according to the cause of death: (i) lethal intoxication by the sum of amitriptyline and nortriptyline or nortriptyline alone, (ii) lethal intoxication by the drugs in combination with other drugs, and (iii) the cause of death was not influenced by amitriptyline and/or nortriptyline. A positive correlation between blood and brain concentrations was found with a Spearman coefficient of 0.98. In 42 cases, where both drugs were detected, the 10-90 percentiles in brain tissue ranged from 0.17-9.1 mg/kg (median: 0.78 mg/kg) for amitriptyline and 0.22-5.0 mg/kg (median: 1.43 mg/kg) for nortriptyline across all classes. In 11 cases where only nortriptyline was detected, the percentiles ranged from 0.32-7.2 mg/kg (median: 0.28 mg/kg) in brain tissue. A median brain-blood ratio of 3.4 was found for amitriptyline, 8.5 for nortriptyline as a metabolite of amitriptyline and 9.7 for nortriptyline as an individual ingested drug. No significant difference was found between the different classes. The obtained brain concentrations and brain-blood ratio can contribute to the alternative or complementary use of brain tissue for future toxicological investigations.