Postmortem Quetiapine Reference Concentrations in Brain and Blood

TY - JOUR

T1 - Postmortem Quetiapine Reference Concentrations in Brain and Blood

AU - Skov, Louise

AU - Johansen, Sys Stybe

AU - Linnet, Kristian

PY - 2015/9

Y1 - 2015/9

N2 - Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N = 36), the 10-90 percentiles for quetiapine concentrations in brain tissue were 0.030-1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10-90 percentile values were 0.007-0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain-blood ratio 10-90 percentiles of 2.31-6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N = 5), the median value in brain tissue of 8.02 mg/kg (range 2.69-22.98 mg/kg) was more than 15 times higher than the median of the nontoxic values, and about the same relationship occurred for blood with a median of 3.19 mg/kg (range 1.00-6.90 mg/kg). The brain-blood ratios for toxic concentrations were in the range of 2.08-6.05, which correspond to those of the nontoxic concentrations. A single case, where quetiapine was ruled as the sole cause of death, a suicide by quetiapine overdose, had an even higher value of 25.74 mg/kg in brain tissue. The blood concentration was 8.99 mg/kg, giving a brain-blood ratio of 2.86. Thus, on average the brain concentrations were about four times the blood concentrations. The brain concentrations of quetiapine observed in cases, where quetiapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available. The recorded concentrations, where quetiapine was contributing to death, give an indication of likely toxic concentrations.

AB - Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N = 36), the 10-90 percentiles for quetiapine concentrations in brain tissue were 0.030-1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10-90 percentile values were 0.007-0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain-blood ratio 10-90 percentiles of 2.31-6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N = 5), the median value in brain tissue of 8.02 mg/kg (range 2.69-22.98 mg/kg) was more than 15 times higher than the median of the nontoxic values, and about the same relationship occurred for blood with a median of 3.19 mg/kg (range 1.00-6.90 mg/kg). The brain-blood ratios for toxic concentrations were in the range of 2.08-6.05, which correspond to those of the nontoxic concentrations. A single case, where quetiapine was ruled as the sole cause of death, a suicide by quetiapine overdose, had an even higher value of 25.74 mg/kg in brain tissue. The blood concentration was 8.99 mg/kg, giving a brain-blood ratio of 2.86. Thus, on average the brain concentrations were about four times the blood concentrations. The brain concentrations of quetiapine observed in cases, where quetiapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available. The recorded concentrations, where quetiapine was contributing to death, give an indication of likely toxic concentrations.

U2 - 10.1093/jat/bkv072

DO - 10.1093/jat/bkv072

M3 - Journal article

C2 - 26159868

SN - 0146-4760

VL - 39

SP - 557

EP - 561

JO - Journal of Analytical Toxicology

JF - Journal of Analytical Toxicology

IS - 7

ER -