Detecting diphenhydramine in a child’s postmortem blood did not automatically establish fatal poisoning. A seven-case series included two deaths attributed wholly or partly to diphenhydramine and five deaths in which the finding was considered incidental. The concentrations informed the investigations but did not supply a universal pediatric lethal cutoff.
How the seven cases were selected
Wallage and Elliot reviewed Ontario Centre of Forensic Sciences cases from 2016–2022. They searched deaths under five years of age with diphenhydramine detected and added selected older children through database searching and author involvement in investigations. The resulting children were four months to eight years old: three males and four females.
This was a selected positive-case series, not a population survey or a controlled dosing study. It could describe findings in these deaths but could not calculate a child’s probability of dying at a particular concentration.
Blood site and preservation mattered
Specimens were collected at autopsy. Blood and urine were placed in tubes containing sodium fluoride and sodium citrate. Femoral blood was available in three older children; only heart blood was submitted in four younger children. The report did not establish a uniform death-to-autopsy interval for all seven.
Diphenhydramine ranged from 0.051 to 2.6 mg/L. In the two six-year-old children whose deaths were attributed to toxicity, femoral concentrations were 1.2 and 2.6 mg/L. The first death involved combined diphenhydramine and ethanol toxicity. The second case had obvious decomposition and limited specimen volume.
The five incidental detections were 0.11 mg/L in femoral blood and 0.051–0.46 mg/L in heart blood. Their causes of death were natural. These heart and femoral observations should not be pooled into a validated concentration boundary separating safe from fatal exposure.
Not every case had the same analytical evidence
The principal targeted LC–MS/MS method used a deuterated internal standard, two diphenhydramine transitions and detection and quantification limits of 0.0125 and 0.025 mg/L, respectively. One older analytical method had corresponding limits of 0.0625 and 0.125 mg/L.
Identification was confirmed using LC-QTOF-MS or GC-NPD-MS in six cases. Limited volume in case 3 allowed only duplicate diphenhydramine quantification, reported as the average; orthogonal identity confirmation was not performed. Duplicate quantitative measurements were not equivalent to the broader confirmation and screening available in the other cases.
Product identity did not reveal the administered dose
Scene or treatment information identified diphenhydramine products in three cases and dimenhydrinate products in three. Dimenhydrinate can yield detectable diphenhydramine, so the measured analyte did not uniquely identify a diphenhydramine-only preparation.
The two toxicity deaths involved adult sleep-aid products, but quantities ingested were unknown. The report did not reconstruct doses from the blood values. Nor did it establish the extent of redistribution in either individual.
What can be concluded in a new case?
Preserve the concentration, anatomical collection site, decomposition status, analytical scope and documented product history. Consider natural disease and co-detected substances alongside the drug finding. A higher value is evidence to investigate, not an automatic mechanism-of-death diagnosis.
The series adds pediatric case observations without proving an adult threshold can be transferred to children or supplying a new universal pediatric threshold. The same distinction between concentration and recovered dose is discussed in postmortem pregabalin interpretation.
Primary source
Wallage HR, Elliot M. Postmortem diphenhydramine blood concentrations in children. Journal of Analytical Toxicology. 2025;49:129–133. doi:10.1093/jat/bkae084.
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