A brain–blood ratio near three can help place a postmortem quetiapine result in the context of comparable autopsy findings. It cannot supply an exact blood concentration when blood is missing, recover the concentration during life, or decide whether quetiapine caused death. A 2026 Copenhagen study found a median ratio of 3.0 in 226 quetiapine cases, with substantial variation around that median.
What specimens produced the reference data?
Van der Meer and colleagues retrospectively reviewed 466 autopsy cases investigated from late 2014 to early 2026. Inclusion required quantification in both blood and brain of at least one of four antipsychotics. Quetiapine accounted for 226 cases; the other drug groups were not separate, mutually exclusive populations.
Bodies were refrigerated at 5°C on arrival, and autopsy usually occurred within four days of arrival. That interval is not a documented death-to-autopsy interval. The investigators lacked the postmortem-interval information needed to assess redistribution over time.
Femoral blood was collected without ligation of the iliac vein, in one or two 4–8 mL tubes containing 100 mg sodium fluoride and 22.5 mg potassium oxalate. Brain specimens were 5–20 g portions of frontal-lobe cerebral cortex. For analysis, 500 mg of grey matter was manually separated and homogenized with water at 1:3. Biological material was stored at −20°C before analysis.
The median describes a distribution, not a fixed conversion
Across the quetiapine cases, median blood concentration was 0.10 mg/kg, with 10th–90th percentiles of 0.015–1.5 mg/kg. Median brain concentration was 0.34 mg/kg, with corresponding percentiles of 0.037–4.1 mg/kg. The median of the individual brain–blood ratios was 3.0, with 10th–90th percentiles of 1.5–5.0.
These percentile intervals describe the middle 80% of observations; they are neither full observed ranges nor confidence intervals. Also, dividing the two group medians is not the same calculation as taking the median of individual paired ratios.
Consider an illustrative brain result of 3 mg/kg. Dividing by three yields a numerical estimate of 1 mg/kg blood, but does not turn that estimate into a measured specimen result. The observed variation in ratios alone prevents calling that reconstruction exact. Nor was the study a validation of individual blood prediction from brain tissue.
Did the ratio distinguish fatal involvement?
The authors classified five quetiapine cases as sole-cause intoxications, 28 as contributing with other drugs or disease, and 193 as cases without quetiapine contribution. Combining the first two categories gave 33 cases with an attributed role in death.
In those 33 cases, median brain concentration was 2.9 mg/kg and median blood concentration was 0.74 mg/kg. In the 193 cases without attributed contribution, the medians were 0.26 and 0.088 mg/kg, respectively. However, the brain–blood ratio medians were much closer: 3.3 versus 2.9. The study reported no statistically significant differences in ratios between the causal categories for any of the four drugs.
That null finding does not establish that the categories were identical. It does show why a ratio near three is not a demonstrated diagnostic boundary between poisoning and incidental detection. The authors also described overlapping concentrations across causal categories.
Quantification had analytical support and tissue limits
Testing used automated solid-phase extraction followed by UHPLC–MS/MS, deuterated internal standards, blood-based calibrators, and quality controls in blood and brain. The reported quetiapine measurement range was 0.005–0.20 mg/kg. Brain quality control at 0.25 mg/kg had a coefficient of variation of 10.2% across 91 measurements; blood controls at 0.01 and 0.5 mg/kg had coefficients of variation of 10.7% and 7.5%.
These performance data concern the analytical procedure. They do not eliminate biological variation or establish that all brain samples have equivalent composition. In advanced decomposition, grey and white matter could not always be separated, and mixed tissue was analyzed. The authors identified tissue composition, matrix effects, extraction efficiency and blood-based calibration as relevant uncertainties.
How should the result be used?
Retain the anatomical brain region, tissue preparation, units, collection conditions and method when comparing a case with this dataset. A complementary brain result can be valuable when blood is unavailable, but should remain identified as a brain measurement. It is not a direct measure of unbound drug at a receptor, observed impairment, ingested dose or antemortem concentration.
For related specimen issues, see the limits of interpreting THC in brain tissue and why similarity between two postmortem specimens does not establish an antemortem concentration.
Primary source
van der Meer MZ, Rasmussen BS, Nedahl M, Nielsen MKK. From blood to brain: postmortem brain concentrations and brain–blood ratios of chlorprothixene, clozapine, olanzapine, and quetiapine. Journal of Analytical Toxicology. 2026;50(7):bkag065. doi:10.1093/jat/bkag065.
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