A published 44-drug redistribution table was not validated by paired antemortem and postmortem measurements for all 44 drugs. McIntyre’s 2016 study compared theoretical factors with 13 observations involving nine drugs from nine cases. The statistically significant relationship supported further investigation, but did not establish precise individual reconstruction across the entire table.
The model and the measured factor were different
The measured factor, F, was the postmortem peripheral whole-blood concentration divided by the corresponding antemortem whole-blood concentration. The theoretical factor, Ft, was calculated from a drug’s characteristic liver/peripheral-blood ratio.
The source dataset summarized median liver/peripheral ratios for 44 drugs from 867 cases. Those 867 cases supplied reference distribution information; they were not 867 people with paired blood specimens collected during life and after death.
The proposed use was to estimate an earlier whole-blood concentration by dividing the postmortem peripheral result by the factor. That proposed calculation must not be mistaken for a directly measured earlier concentration.
What did the thirteen examples show?
The paired comparison involved 13 drug observations from nine cases. Some people supplied more than one drug observation, so the dataset was not thirteen independent decedents. Antemortem specimens were collected one to 36 minutes before death. The death-to-autopsy interval was 5.2–42 hours, averaging 17 hours.
The relationship between measured and theoretical factors was statistically significant: R² = 0.7006, p = 0.001. That association was not a case-specific prediction interval or a demonstration of equivalent accuracy for every drug.
For example, the fentanyl observation had antemortem and postmortem concentrations of 0.0014 and 0.0016 mg/L, respectively. The table reported a measured factor of 1.1 and theoretical factor of 1.5. A quetiapine observation was 0.15 mg/L before death and 0.24 mg/L afterward, giving a measured factor of 1.6 versus theoretical 2.0. The factors did not match exactly even in these closely timed cases.
Collection conditions restricted the application
The study excluded obvious decomposition. Its described collection procedure used right-lobe liver tissue and peripheral blood from the visually identified common iliac vein. The upper iliac vein was usually not clamped, allowing potential contribution from more proximal blood. It should not be silently relabeled as an isolated femoral-vein specimen.
Blood was collected into fluoride/oxalate tubes; liver had no preservative, and specimens were stored at 4°C. Screening included immunoassay and chromatographic procedures, followed by specific confirmation and quantitation. Different drugs required different analytical methods. The article did not provide one common numerical detection limit, quantification limit or precision value for all nine paired analytes.
What remained unverified?
The author explicitly stated that the same relationship lacked direct evidence for the other 35 drugs. Their theoretical entries were hypotheses requiring further verification, not observed before-and-after changes.
The paper also cautioned against extension to prolonged postmortem intervals, decomposition, incomplete drug distribution in acute overdose, and incompatible blood or liver collection sites. It found no obvious effect of interval within its small comparison but acknowledged inadequate numbers to resolve that question.
A drug ranking can assist interpretation without supplying an exact correction for every individual. Before applying any factor, reviewers need to examine independent validation, sample comparability, prediction uncertainty and the clinical interval before death. Neither the factor nor a reconstructed number establishes impairment or cause of death.
The importance of preserving individual exceptions is illustrated by the repeated hydrocodone liver-to-blood outlier.
Primary source
McIntyre IM. Analytical data supporting the “theoretical” postmortem redistribution factor (Ft): a new model to evaluate postmortem redistribution. Forensic Sciences Research. 2016;1(1):33–37. doi:10.1080/20961790.2016.1253255.
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