Detection of Acetaminophen–Protein Adducts in Decedents with Suspected Opioid–Acetaminophen Combination Product Overdose

Acetaminophen overdose is a leading cause of drug‐induced liver failure in the United States. Acetaminophen–protein adducts have been suggested as a biomarker of hepatotoxicity. The purpose of this study was to determine whether protein‐derived acetaminophen–protein adducts are quantifiable in postmortem samples. Heart blood, femoral blood, and liver tissue were collected at autopsy from 22 decedents suspected of opioid–acetaminophen overdose. Samples were assayed for protein‐derived acetaminophen–protein adducts, acetaminophen, and selected opioids found in combination products containing acetaminophen. Protein‐derived APAP‐CYS was detected in 17 of 22 decedents and was measurable in blood that was not degraded or hemolyzed. Heart blood concentrations ranged from 11 ng/mL (0.1 μM) to 7817 ng/mL (28.9 μM). Protein‐derived acetaminophen–protein adducts were detectable in liver tissue for 20 of 22 decedents. Liver histology was also performed for all decedents, and no evidence of centrilobular hepatic necrosis was observed.