No. A negative preliminary autopsy drug screen does not exclude exposure to medication, and a negative result from one instrumental workflow does not exclude every drug. A retrospective study of 2,996 forensic autopsies found additional drugs through broader GC–MS screening and selected LC–MS/MS reanalysis. The findings concern the scope and performance of particular procedures, not a universal failure rate for toxicology.
What did the study review?
Tominaga and colleagues reviewed routine work at an Osaka forensic institute from January 1996 through June 2014. Cases without adequate specimens because of advanced decomposition or skeletonization were excluded. This was an institutional autopsy series, not a random sample of deaths in the general population.
On-site immunoassays and GC–MS were used in the routine program. In selected cases during the final four years, another laboratory performed additional GC–MS and LC–MS/MS testing. Reanalysis was prompted by discrepancies or continued suspicion of drug exposure despite negative screening, when suitable specimens remained available.
Blood and several additional matrices were routinely collected, including peripheral blood, urine, pericardial fluid, cerebrospinal fluid, bone marrow aspirate, bile and stomach contents. Alternative effusions were used when necessary. Specimens were stored at −20°C after preliminary immunoassay testing. The paper does not supply one uniform collection site or death-to-sampling interval for every reported finding.
What broader testing added
GC–MS detected drugs in 486 cases, or 16.2% of the series. The investigators reported 2,440 cases with negative preliminary immunoassays and identified additional drugs by GC–MS in 218 cases—7.3% of all 2,996 cases. These included medications outside, or inadequately represented by, the preliminary panels, such as antidepressants, acetaminophen and salicylic acid.
The denominator matters. The reported 7.3% is a proportion of the complete autopsy series; it should not be described as the sensitivity of an immunoassay for every drug. A medication outside a panel is a different problem from a panel target present above its threshold but missed.
Selected LC–MS/MS reanalysis also showed that the original GC–MS workflow was not an exhaustive reference. In 25 of 32 cases selected for discordant benzodiazepine findings, LC–MS/MS detected low concentrations of benzodiazepines or their metabolites. Seven had no such detection. The detailed results refine the abstract’s broader description of the 32-case reanalysis.
Why those 32 cases do not measure routine sensitivity
These cases were selected because the results or circumstances already raised concern. They were not a random validation sample of all negative GC–MS specimens. Consequently, 25 of 32 cannot be applied as an expected missed-detection rate in another laboratory.
The authors reported GC–MS quantitative precision below 10% for the drugs and specimens evaluated. That describes repeatability within the studied procedure; it does not establish detection of every possible substance. Some LC–MS/MS findings were explicitly semiquantitative and should not be rewritten as definitive quantitative blood concentrations.
The analytical instruments and screening arrangements also changed across the 18.5-year period. Apparent changes in detection over time therefore require attention to ascertainment and methodology, as well as possible changes in exposure.
Detection did not automatically establish poisoning
Of the 486 GC–MS drug-positive cases, 123 were classified as fatal intoxications. Drugs were also detected in deaths from other causes. Drug-category counts overlapped because more than one drug could be present. Neither a positive result nor a count of co-detected medications independently establishes impairment or a causal contribution.
A case review should identify the panel, analytes, matrices, reporting thresholds, extraction and instrumental methods, and reasons for any additional testing. For another specimen-specific screening question, see vitreous humor versus blood for postmortem drug screening.
Primary source
Tominaga M, Michiue T, Inamori-Kawamoto O, et al. Efficacy of drug screening in forensic autopsy: Retrospective investigation of routine toxicological findings. Legal Medicine. 2015;17(3):172–176. doi:10.1016/j.legalmed.2015.01.001.
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