FORENSIC TOXICOLOGY.NETOkorie Okorocha, J.D., M.S., M.S.Forensic Toxicology Expert Witness

EVIDENCE LIBRARY

Postmortem Drug Concentrations: Why Reference Ranges Overlap

By forensic toxicology working group members

Why therapeutic, toxic and fatal postmortem drug ranges overlap—and how specimen site, redistribution, tolerance, and co-intoxicants change interpretation.

Technical reference from THE OKOROCHA FIRM, with scientific editorial direction by Okorie Okorocha, M.S., M.S., Esq., attorney and forensic toxicologist. Postmortem drug concentrations should be interpreted as evidence within a case, not as automatic labels of “therapeutic,” “toxic,” or “fatal.” The clinical idea of a therapeutic window should not be treated as a forensic verdict; seeTDM vs TCI: Therapeutic Ranges in Forensic Toxicology. The same measured concentration can appear in different outcome groups because of differences in specimen site, postmortem redistribution, tolerance, co-intoxicants, survival interval, treatment, analytical method, and individual pharmacology all affect interpretation.

Quick answer

Can a published therapeutic, toxic, or fatal concentration range determine whether a drug caused death? No. Reference ranges are useful context, but they are not bright-line verdicts. Postmortem concentrations often overlap across fatal and nonfatal circumstances, and values measured after death may not equal concentrations at the time toxicity developed. A defensible opinion integrates the concentration with specimen source, collection conditions, autopsy findings, medical history, tolerance, other drugs, scene evidence, and the analytical record.

What reference concentration tables actually represent

Forensic references frequently summarize concentrations reported in therapeutic use, intoxications, and fatalities. Those compilations can help a reviewer recognize whether a result is broadly consistent with concentrations reported elsewhere. They are most useful as comparison data, not as a substitute for case analysis.

Three cautions are fundamental. First, the source populations may differ: living patients, impaired drivers, hospital overdose patients, and medical-examiner cases are not interchangeable. Second, the specimen matrices may differ: serum or plasma concentrations should not automatically be compared with postmortem whole-blood concentrations. Third, a range compiled from published cases inherits the selection criteria, analytical methods, and case classifications used by those reports.

Why “therapeutic” and “fatal” ranges can overlap

Tolerance changes the concentration-effect relationship

A person with repeated exposure may tolerate concentrations that would produce greater effects in an opioid-naive, sedative-naive, or stimulant-naive person. Conversely, advanced age, disease, genetic variation, drug interactions, or reduced clearance may increase susceptibility at concentrations that fall within ranges sometimes described as therapeutic.

Polydrug exposure can lower the concentration needed for a fatal outcome

Many forensic deaths involve multiple central nervous system depressants or other interacting substances. An opioid concentration that is not extraordinary in isolation may become much more consequential when combined with alcohol, benzodiazepines, sedating antihistamines, gabapentinoids, or other respiratory depressants. The relevant question is therefore not simply whether one analyte exceeded a tabulated number.

Postmortem redistribution can change blood concentrations after death

After circulation stops, drugs may move between tissues and blood. Lipophilic and basic compounds with large apparent volumes of distribution are often of particular concern, but redistribution is drug-specific and case-specific. Central blood can be more affected by diffusion from nearby organs and gastric contents. Peripheral blood is generally preferred for quantitative interpretation when properly collected, but peripheral sampling does not eliminate every postmortem change.

For the sampling-site problem in more detail, see Central vs. Peripheral Blood in Postmortem Toxicology and Postmortem Blood Sampling Sites: Interpretation Guide.

Matrix matters

Whole blood, plasma, serum, vitreous humor, urine, liver, and other tissues can contain materially different concentrations. A serum value from a living patient should not be treated as interchangeable with a postmortem femoral whole-blood result. Even within blood, the exact collection site can matter. Review Biological Matrices in Forensic Toxicology and Whole Blood vs. Plasma in Forensic Toxicology.

Survival time and medical treatment can change the result

If a person survives for hours after exposure, absorption, distribution, metabolism, elimination, intravenous fluids, transfusion, antidotes, resuscitation, and organ failure may alter the measured concentration. A postmortem value therefore reflects the biology and interventions that occurred before collection as well as processes after death.

A 2026 oxycodone meta-analysis illustrates the overlap problem

A 2026 systematic review and meta-analysis of human postmortem oxycodone data emphasized that peripheral-blood concentrations were highly variable and substantially overlapped across forensic contexts. Fatal intoxication cases tended to have higher concentrations in aggregate, but mixed-drug deaths, tolerance, prescription history, postmortem interval, and other factors materially complicated interpretation. This is exactly why group-level concentration distributions should not be converted into an individual bright-line rule.

See Postmortem Oxycodone Toxicology: A Systematic Review and Meta-Analysis of Concentrations and Interpretative Markers (2026).

Questions to ask before relying on a concentration table

  1. What specimen was tested? Identify whole blood, serum, plasma, urine, vitreous, tissue, or another matrix.
  2. Where was postmortem blood collected? Femoral, iliac, subclavian, heart, and cavity blood should not be assumed equivalent.
  3. When was it collected? Establish the death-to-collection interval and any storage delay.
  4. Was the specimen preserved? Review tube type, preservative, temperature, freeze-thaw history, and specimen integrity.
  5. Was the method quantitative and validated for that matrix? Review calibration range, limits, controls, uncertainty, dilution, and identification criteria.
  6. What other substances were present? Evaluate additive or synergistic pharmacology rather than isolating one number.
  7. Was the person tolerant? Prescription records, treatment history, refill patterns, toxicology history, and collateral evidence may matter.
  8. Were resuscitation or medical interventions performed? Fluids, transfusions, medications, antidotes, and prolonged survival can affect interpretation.
  9. How was the comparison range derived? Determine whether the cited source used living or postmortem subjects, which matrix was tested, and how “fatal” cases were classified.
  10. Does the pathology support the proposed mechanism? Cause-of-death interpretation should fit the autopsy, scene, clinical history, and competing explanations.

What a concentration can establish

When produced by a validated quantitative method, a concentration can establish how much of the measured analyte was present in the tested specimen at the time represented by that specimen, subject to analytical uncertainty and specimen integrity. It may also support or weaken a pharmacological hypothesis when interpreted with the rest of the record.

What a concentration cannot establish by itself

A single postmortem concentration ordinarily cannot, by itself, establish the exact dose, exact time of use, degree of impairment before death, tolerance, intent, survival interval, or whether the drug independently caused death. Those conclusions require additional evidence and, in some cases, remain uncertain even after a complete investigation.

Laboratory records that improve the interpretation

The final toxicology report is only the starting point. Important records may include specimen inventory and collection documentation; chain of custody; extraction and preparation records; calibrators, controls, and blanks; chromatograms and mass-spectrometric identification data; dilution records; repeat analyses; uncertainty information; method validation; instrument maintenance; analyst review; and the laboratory’s reporting policy. See the Toxicology Laboratory Records Evidence Review Checklist.

Frequently asked questions

If a value is inside a published “fatal range,” does that prove the drug caused death?

No. It supports comparison with reported fatalities but does not resolve tolerance, co-intoxicants, redistribution, specimen site, medical treatment, competing causes, or the quality of the underlying reference data.

If a value is inside a “therapeutic range,” does that exclude toxicity?

No. Susceptibility varies, interactions matter, and ranges developed in living patients may not transfer directly to postmortem specimens. A concentration described as therapeutic in one context can still be relevant in another.

Is femoral blood always reliable?

Peripheral femoral blood is generally preferred for postmortem quantitative interpretation, but it is not immune to sampling error, contamination, redistribution, degradation, or case-specific effects.

Should central-to-peripheral ratios be used as universal correction factors?

No. Such ratios can provide context but vary by drug, sampling method, postmortem interval, case circumstances, and study design. They should not be treated as universal mathematical corrections.

Scientific grounding

General scientific reference material only. It is not a case-specific expert opinion, medical advice, or a substitute for review of the complete toxicology, pathology, and investigative record.