A drug’s volume of distribution can inform concern about postmortem redistribution, but it cannot reliably rank the change expected in an individual death. In a 129-case study, drugs with relatively small reported distribution volumes sometimes had larger central-to-peripheral concentration ratios than drugs with much larger volumes. The study measured differences between sampling sites; it did not measure each person’s change from life to death.
What the study actually compared
Han and colleagues examined 129 selected drug-related cases investigated by South Korea’s National Forensic Service during 2006–2009. One to six drugs were detected per case, and the study reported results for 76 drugs. This was not a series of 129 observations for every drug. Thirty-three drugs had results from at least two cases; the remaining drugs had only one case each.
The collection details matter. Femoral venous blood was obtained after ligation to reduce drawing blood from central vessels. The specimen called “cardiac blood” in the article was collected from the inferior vena cava after the chest and abdomen were opened. Paired specimens were stored in 50-mL plastic tubes at −20°C until analysis. The reported average interval from arrival at the facility to collection was approximately three hours, which is not the interval from death to collection.
Drugs were quantified by GC–MS or LC–MS/MS. The authors referred to earlier publications and laboratory procedures for method validation. The paper does not supply a complete analyte-specific validation dataset that would allow a reader to assign one analytical uncertainty to all 76 drugs.
The exceptions to a simple ranking rule
Volume of distribution describes the relationship between the amount of drug in the body and its blood or plasma concentration under the relevant pharmacokinetic conditions. It is not a direct measurement of how much drug will move after death. The authors discussed a distribution volume above approximately 3–4 L/kg as a reason for concern, but their observations showed why that cannot function as a universal dividing line.
| Drug | Distribution volume discussed in the paper | Mean central/femoral ratio in this series | Cases |
|---|---|---|---|
| Codeine | 2.2 L/kg | 4.90; range 1.14–8.67 | 2 |
| Zolpidem | 0.6 L/kg | 3.74; range 0.67–13.25 | 17 |
| Nortriptyline | 20 L/kg | 2.01; range 0.40–5.63 | 12 |
| Sertraline | 20 L/kg | 1.73; range 1.00–2.53 | 4 |
| Amitriptyline | 12 L/kg | 1.36; range 0.73–2.50 | 13 |
These are descriptive comparisons, not a statistically validated ranking model. The distribution-volume values were discussed as drug properties, not measured separately in these decedents. Codeine’s apparently large average rests on just two cases. Zolpidem’s range includes a ratio below one and a value above thirteen. Neither average is a dependable multiplier for a new case.
A site ratio is not an antemortem correction
The numerator and denominator were both postmortem measurements. No antemortem drug concentrations were available for any case, and the death-to-collection interval was unavailable for most cases. There were no earlier serial specimens with which to establish the direction or speed of change.
Accordingly, dividing a central result by the published mean ratio would estimate neither a validated femoral concentration for that person nor the concentration during life. A ratio near one also cannot show that both sites remained unchanged. This distinction is illustrated further in our discussion of fentanyl specimen ratios near one.
How the findings help a case review
The practical value is to identify an assumption that needs evidence. A low distribution volume does not justify treating a central specimen as unaffected by postmortem processes. A high volume does not supply a numerical correction. The actual collection site, ligation technique, specimen history, analyte and available comparison specimens remain necessary parts of interpretation.
Detection establishes an analytical finding in the tested specimen. Even a well-measured concentration and a plausible redistribution mechanism do not independently establish impairment, the ingested dose or cause of death. A separate hydrocodone study with an influential outlier illustrates why individual observations should remain visible behind summary statistics.
Primary source
Han E, Kim E, Hong H, Jeong S, Kim J, In S, Chung H, Lee S. Evaluation of postmortem redistribution phenomena for commonly encountered drugs. Forensic Science International. 2012;219:265–271. https://doi.org/10.1016/j.forsciint.2012.01.016.
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