Do Postmortem Drug Concentrations Always Rise With Delayed Sampling?

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Postmortem drug concentrations do not invariably rise as sampling is delayed. Prouty and Anderson documented increases, decreases and relatively stable results, sometimes at different sites in the same decedent. Their sequential observations support attention to collection time; they do not supply a dependable hourly correction back to death.

Nine cases with repeated anatomical sampling

Table 1 of the 1990 study contains nine distinct cases selected because an antidepressant was present. Both drug-related and nondrug deaths were included. Multiple compounds, sites and collection phases within one case are repeated observations, not additional independent decedents.

Phase I included some or all of the left and right subclavian veins, heart chambers and femoral veins. The chest plate had been removed before that collection. Phase II occurred at least two hours later; occasional Phase III collections followed at least another two hours later. Tissues and other fluids were collected with the final autopsy specimens. Intervals differed among cases.

The tables distinguish “found dead to Phase I” from the interval between sampling phases. Time since discovery is not necessarily time since death, especially when death was unwitnessed. Nor was an initial postmortem collection a specimen obtained while the person was alive.

One case illustrates why the anatomical site matters over time

In case A-1087, amoxapine in left heart blood increased from 3.9 to 4.6 to 7.0 mg/L over three phases. Left subclavian blood measured 2.0, 1.7 and 2.0 mg/L across the same phases. Left femoral blood increased from 2.6 to 3.0 to 4.7 mg/L.

The first collection was 17 hours after the person was found dead. Four hours separated Phases I and II, and two hours separated Phases II and III. These observations do not establish that each vessel followed the same trajectory or that a single increase rate described the body.

In case A-1541, doxepin in right subclavian blood decreased from 6.7 to 4.9 mg/L, while right heart blood increased from 4.2 to 5.0 mg/L. The phase interval was four hours; the first phase was 9.5 hours after discovery. Selecting only the rising result would omit a material finding from the same case.

Earlier field blood was also postmortem blood

A separate part of the investigation compared field blood collected by cardiac puncture with autopsy heart and femoral specimens collected several hours later. The authors described 12 cases involving 17 drugs. Case-specific standardized intervals were not supplied for calculating a formation or redistribution rate.

For example, amitriptyline in case B-0325 measured 0.48 mg/L in field heart blood, 2.1 mg/L in autopsy heart blood and 0.91 mg/L in autopsy femoral blood. This demonstrates a difference across collection events. It does not independently reveal the concentration during life. Some paired values in the field table were nearly unchanged or identical at the reported precision, so a general increase pattern should not be recast as a material rise in every analyte.

What the analytical methods establish

The investigators used antidepressant assays that included HPLC and gas chromatographic methods for most other drugs. Apart from certain insufficient-volume vitreous specimens, analyses were performed in duplicate; discrepancies exceeding 10% triggered repeat analysis. Typical coefficients of variation were below 10%.

The serial case observations were not presented as a validated kinetic model with drug-specific prediction intervals. The paper supplies no universal hourly slope, and these examples should not be described as statistically significant changes merely because their numerical values differ.

Implications for reviewing a toxicology result

Keep collection time, site and specimen identity attached to every number. A later result cannot be substituted silently for an earlier one, and a postmortem series cannot establish dose, impairment or cause of death without additional evidence. Our discussion of comparisons with earlier clinical specimens explains the separate problem of relating autopsy blood to a predeath measurement.

Primary source

Prouty RW, Anderson WH. The Forensic Science Implications of Site and Temporal Influences on Postmortem Blood-Drug Concentrations. Journal of Forensic Sciences. 1990;35(2):243–270. doi:10.1520/JFS12828J.

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