Femoral blood collected at autopsy cannot automatically be treated as the concentration present before death. In a historical series, Hilberg and colleagues found substantial differences between earlier serum and later femoral blood for tricyclic antidepressants. Peripheral sampling helped limit some problems associated with heart blood, but did not eliminate postmortem change.
What the study actually compared
The 1999 paper described ten human cases overall. Eight involved comparisons with ante- or perimortem serum; two additional cases involved early postmortem blood. The tricyclic analysis of femoral blood pooled 11 drug or metabolite observations from six people, not 11 independent decedents. The compounds included amitriptyline, nortriptyline, imipramine and desipramine.
Autopsies in the overall series occurred at a median of two days after death, with a reported range of one to seven days. Femoral blood was obtained through a groin incision while the lower limb was elevated, drained into a clean scoop, and transferred to tubes containing potassium fluoride. The collectors tried to avoid blood from the iliac veins above. Samples were stored at −20°C until analysis. Heart specimens, where available, came from an unspecified chamber.
A higher postmortem result was common, but not universal
The pooled median femoral-blood-to-earlier-serum ratio for tricyclic compounds was 3.3, with a reported 95% reference range of 1.1–6.0. That reference range describes the pooled observations; it is not a validated prediction interval for any new individual.
In one amitriptyline case, serum measured 2.0 μmol/L and femoral blood collected at autopsy two days after death measured 12 μmol/L, a ratio of 6.0. Nortriptyline in the same case changed from 1.3 to 6.0 μmol/L. In another case, nortriptyline was 2.0 μmol/L in perimortem serum and 1.8 μmol/L in femoral blood the following day, a ratio of 0.9. The exception matters: the study did not establish an inevitable increase of a fixed size.
The denominator was serum, not earlier femoral whole blood
A ratio across both time and matrix cannot isolate redistribution alone. The authors discussed differences in drug partitioning between serum or plasma and whole blood, as well as resuscitation and sampling technique. They considered matrix partitioning insufficient to explain the full tricyclic differences, but that does not turn every observed ratio into a pure measure of postmortem movement.
Quantitative analysis used HPLC with ultraviolet detection. The described method had a 0.2 μmol/L detection limit, calibration from 0.2–10 μmol/L, recovery above 80% at 1 and 10 μmol/L, and within-run precision below 10% CV. Some case concentrations exceeded the stated calibration range; the paper does not explain every such result’s dilution or extended-range procedure. A modern case review should obtain those laboratory details rather than presume them.
What this evidence supports in a death investigation
The series supports caution when an autopsy concentration is compared directly with a therapeutic serum range. It does not supply a universal divisor of 3.3, prove an administered dose, or establish cause of death from the concentration alone. Treatment, elapsed time, other drugs, pathology and the original analytical records remain material.
For the distinct problem of comparing two postmortem sites, see central-to-peripheral blood ratios. A site ratio and a postmortem-to-antemortem comparison answer different questions.
Primary source
Hilberg T, Rogde S, Mørland J. Postmortem Drug Redistribution—Human Cases Related to Results in Experimental Animals. Journal of Forensic Sciences. 1999;44(1):3–9. doi:10.1520/JFS14404J.
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