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.
['Thomas|Karen C|KC|', 'Wilkins|Diana G|DG|', 'Curry|Steven C|SC|', 'Grey|Todd C|TC|', 'Andrenyak|David M|DM|', 'McGill|Lawrence D|LD|', 'Rollins|Douglas E|DE|']
D000082:Acetaminophen D018712:Analgesics, Non-Narcotic D000701:Analgesics, Opioid D056486:Chemical and Drug Induced Liver Injury D062787:Drug Overdose D006801:Humans D008099:Liver D011506:Proteins
acetaminophen-protein adducts acetaminophen protein-derived APAP-CYS clinical laboratory techniques forensic science postmortem redistribution