title: Detection of Acetaminophen-Protein Adducts in Decedents with Suspected Opioid-Acetaminophen Combination Product Overdose.
abstract: 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.
authors.affiliation: University of Utah Health Care, Salt Lake City, UT. karen.thomas@hsc.utah.edu.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Thomas
authors.affiliation: Center For Human Toxicology, University of Utah, Salt Lake City, UT.|Department of Pathology, University of Utah, Salt Lake City, UT.
authors.forename: Diana G
authors.initials: DG
authors.lastname: Wilkins
authors.affiliation: Department of Medical Toxicology, Banner Good Samaritan Medical Center, University of Arizona College of Medicine-Phoenix, Phoenix, AZ.|Department of Medicine and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine-Phoenix, Phoenix, AZ.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Curry
authors.affiliation: Office of the Medical Examiner, Utah Department of Health, Salt Lake City, UT.
authors.forename: Todd C
authors.initials: TC
authors.lastname: Grey
authors.affiliation: Center For Human Toxicology, University of Utah, Salt Lake City, UT.
authors.forename: David M
authors.initials: DM
authors.lastname: Andrenyak
authors.affiliation: Animal Reference Pathology, Division, ARUP Laboratories, Salt Lake City, UT.
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: McGill
authors.affiliation: Center For Human Toxicology, University of Utah, Salt Lake City, UT.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Rollins
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D018712:Analgesics, Non-Narcotic / Q000506:poisoning*; D000701:Analgesics, Opioid; D056486:Chemical and Drug Induced Liver Injury; D062787:Drug Overdose / Q000175:diagnosis*; D006801:Humans; D008099:Liver; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D011506:Proteins; D000082:Acetaminophen
keywords: acetaminophen; acetaminophen-protein adducts; clinical laboratory techniques; forensic science; postmortem redistribution; protein-derived APAP-CYS