A missing MDMA cardiac-to-femoral ratio can reflect an analytical range limit rather than absence of MDMA. A Dutch postmortem study reported nine cases in which cardiac MDMA exceeded the upper quantitation limit and no subsequent diluted quantification was performed, leaving no numerical MDMA ratio.
Why a positive finding may not yield a usable concentration
de Groot and colleagues reviewed Netherlands Forensic Institute casework from January 2010 through July 2020. Inclusion required a studied compound to be quantified in both femoral and central blood. The amphetamine-group dataset included 112 cases, with 75 amphetamine, 39 MDMA and 35 MDA paired ratios. The same case could contribute more than one analyte.
Screening and quantitative measurement were separate parts of the workflow. Detected compounds underwent quantitative UPLC–MS/MS. A positive analytical finding did not guarantee that both specimens had numerical results within the procedure’s supported quantitative range.
The upper boundary mattered in nine cases
The reported seven-point calibration interval for both MDMA and MDA was 0.005–1 mg/L. In nine of the 35 MDA cases, an MDMA C/P ratio was unavailable because cardiac MDMA was above the upper limit and the laboratory did not subsequently quantify a diluted sample.
A result above an upper limit is not the same as a result equal to that limit. Substituting 1 mg/L as though it were the measured concentration would create an artificial ratio. The paper supplied no exact cardiac concentration for those nine above-range findings from which a numerical ratio could be reconstructed.
A properly supported diluted reanalysis can address an above-range sample, but that additional measurement must actually have occurred. It cannot be supplied retrospectively by assuming the response stayed linear beyond the calibration interval.
Two different reasons for unequal MDMA and MDA counts
Among the 39 MDMA cases with ratios, 26 also had an MDA ratio. In the remaining 13, MDA was not detected and MDMA concentrations were described as low. The authors interpreted MDA as an in-vivo metabolite of MDMA in the included material.
The nine additional MDA cases had a different issue: MDA was quantitatively available, while MDMA’s cardiac concentration exceeded the upper range without diluted quantification. These situations should not be merged into one category called negative testing.
Neither absence of a reported MDA signal nor an unavailable MDMA ratio establishes a known time since use. The study did not validate a detection-pattern clock or a dose reconstruction for these cases.
Collection and method details remain part of the result
Femoral blood was obtained by syringe after targeted dissection and before internal examination. Central blood was obtained from the right atrium or inferior vena cava with the heart in place. Sodium-fluoride/sodium-heparin tubes were stored at −20°C; analysis occurred within three months after collection.
For MDMA, Table 2 reported accuracy deviation −5%, precision 6% and recovery 94%. MDA figures were −11%, 5% and 84%, respectively. These are validation results for the reported quantitative method, not proof of accuracy at an unmeasured concentration above its upper range.
Missing high results can limit a ratio dataset
Requiring two quantified concentrations means the available-ratio population depends partly on analytical coverage. The nine cases demonstrate why a ratio table cannot automatically be read as including every positive specimen or every high-concentration case.
The study did not quantify how these omitted MDMA ratios would have altered the summary distribution. It would therefore also be unwarranted to assert the direction or size of a selection effect without the missing measurements.
What to ask of an above-range report
Preserve the original qualifier, matrix, concentration unit, calibration limits and any dilution record. Distinguish “detected,” “quantified,” “above range” and “not detected.” No numerical ratio, impairment conclusion or cause-of-death inference should be manufactured from a missing concentration.
The corresponding lower-boundary issue is illustrated by quetiapine detected below the quantitation limit.
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.
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