Why a Ratio of Average Cardiac and Femoral Drug Concentrations Is Not a Paired Redistribution Result

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Dividing average cardiac drug concentration by average femoral concentration does not necessarily produce the average paired ratio, especially when the averages come from different people. A Milan autopsy review provides a concrete example: its cardiac and femoral cocaine means used different numbers of available specimens.

The source was a selected casework series

Di Candia and colleagues reviewed 136 cases with requested toxicological analyses among 1,323 autopsies performed during 2018–2019. Samples were collected at autopsy and stored at −20°C. Testing primarily involved femoral blood, cardiac blood, urine and gastric contents, with organs used selectively.

The report used HPLC–MS/MS, GC–MS and headspace analysis as appropriate. Its workflow separated library-based screening, qualitative identification and subsequent quantification using calibration standards. It was not a controlled serial-sampling experiment measuring the same person’s concentration before and after death.

The cocaine averages did not have identical denominators

Table 1 described 15 cocaine acute-intoxication cases in the single-substance category. Cardiac blood concentrations ranged from 0.33 to 19.8 µg/mL, with a reported average of 5.37 µg/mL. Femoral blood ranged from 0.49 to 18.78 µg/mL, with an average of 5.28 µg/mL.

The footnotes specify that the cardiac mean used 13 cases, whereas the femoral mean used 14. The ratio of these published averages is approximately 1.02, displayed as 1.0 in the table. The available-specimen sets were therefore not identical.

This is a materially different calculation from obtaining each decedent’s cardiac/femoral ratio and then summarizing those individual ratios. A ratio of means also weights observations differently from a mean of ratios, even when every person has both specimens.

Similar averages do not establish matching specimens

The closeness of 5.37 and 5.28 µg/mL cannot establish that all paired samples agreed. Aggregate values can conceal individual differences, and missing specimens can alter the comparison further. The table does not provide a validated prediction interval for estimating an individual’s femoral concentration from cardiac blood.

Results for different analytes also should not be combined into one universal conversion factor. The table included a ketamine case with cardiac blood at 5.69 µg/mL and femoral blood at 3.36 µg/mL, a ratio of approximately 1.7. One ketamine pair is descriptive evidence from one person, not a population calibration.

A site ratio is not a time-course measurement

Cardiac and femoral specimens sample different anatomical locations. A comparison between them describes site-dependent concentrations at collection. It does not directly measure the change from antemortem concentration to autopsy concentration.

The Milan series lacked a uniform reported postmortem interval and a paired predeath concentration dataset. A ratio near one therefore did not prove the absence of redistribution, while a ratio above one did not isolate redistribution from every other influence on the specimens.

How to use the table responsibly

Preserve each drug, specimen site, unit and available-sample denominator. Establish whether a published ratio is calculated from individual pairs or aggregate means before applying it to a case. Do not silently treat a missing specimen as zero or as agreement.

The measurements can inform a broader interpretation, but neither an average ratio nor an individual site ratio independently establishes dose, impairment or cause of death. For a separate drug-specific example, see fentanyl ratios near one and the limits of redistribution inference.

Primary source

Di Candia D, Giordano G, Boracchi M, Zoja R. Postmortem forensic toxicology cases: A retrospective review from Milan, Italy. Journal of Forensic Sciences. 2022;67:1640–1650. doi:10.1111/1556-4029.15050.

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