Higher Femoral Amphetamine Concentrations Had Lower Site Ratios: What 75 Autopsies Can Establish

Higher femoral amphetamine concentrations were associated with lower cardiac-to-femoral ratios in a Dutch autopsy study. That finding did not establish that high concentrations were unchanged after death, or provide a formula for reconstructing an individual concentration during life.

Seventy-five amphetamine pairs, not 112 independent pairs

de Groot and colleagues reviewed Netherlands Forensic Institute investigations from January 2010 through July 2020. Their amphetamine-group dataset contained 112 cases involving amphetamine, MDMA or MDA quantified in both blood sites. Amphetamine itself contributed 75 pairs. Cases could contribute more than one analyte.

Femoral blood was obtained by sterile syringe after targeted dissection, before internal examination. Central blood came from the right atrium or inferior vena cava with the heart in place. Sodium-fluoride/sodium-heparin tubes were stored at −20°C and analyzed within three months of collection.

The ratio compared two postmortem sites collected at autopsy. There was no paired antemortem concentration establishing how far either result had moved from the value during life.

What changed across concentration quartiles?

The highest quartile differed from the first and second quartiles in post-hoc comparisons, with p < 0.001 and p = 0.001, respectively. These met the study’s corrected significance threshold of p < 0.0045 for amphetamines. The published concentration boundaries are descriptive divisions of this dataset, not clinical or legal thresholds.

A median ratio of 1.6 did not mean equality between sites. Individual ratios within the highest quartile also crossed one. The association cannot be converted into a rule that every high result has a particular redistribution history.

Short survival was a possible explanation

The authors proposed that a short interval between dosing and death could leave less drug deposited in tissues, reducing the reservoir available to redistribute into central blood. That mechanism was not directly measured in each person. Route of administration could not be determined from the available amphetamine case records and was omitted from the statistical analysis.

The authors considered a high femoral concentration together with a ratio near one suggestive of limited redistribution, particularly if circumstances supported short survival. This remained a contextual inference, not validation of a numerical correction or an exact survival-time estimate.

Method performance and biological interpretation are separate

Routine screening was followed by quantitative UPLC–MS/MS. For amphetamine, the reported calibration limits were 0.005–1 mg/L; Table 2 listed accuracy deviation −11%, precision 7% and recovery 83%. These validation figures describe the measurement procedure. They do not validate the proposed survival-time mechanism or a concentration-to-dose relationship.

No corresponding significant concentration-quartile association was established for MDMA. MDA’s quartile comparison had p = 0.012, which did not meet the corrected threshold. The amphetamine finding should therefore retain its analyte-specific scope.

What should accompany a quoted ratio?

Preserve both original concentrations, collection sites, timing and the available circumstances. Do not divide an individual result by a quartile median to recover a presumed predeath concentration. Detection and a postmortem site ratio do not independently establish impairment or cause of death.

For another site-ratio limitation, see why a fentanyl ratio near one does not exclude postmortem change.

Primary source

de Groot ADE, Borra LCP, van der Hulst R, et al. Postmortem redistribution of amphetamines and benzodiazepines in humans: Important variables that might be influencing the central blood / peripheral blood ratio. Forensic Science International. 2023;353:111876. doi:10.1016/j.forsciint.2023.111876.