Detection of Acetaminophen–Protein Adducts in Decedents with Suspected Opioid–Acetaminophen Combination Product Overdose |
| |
| Authors: | Karen C Thomas PharmD PhD Diana G Wilkins PhD MS Steven C Curry MD Todd C Grey MD David M Andrenyak PhD Lawrence D McGill DVM PhD Douglas E Rollins MD PhD |
| |
| Institution: | 1. University of Utah Health Care, Salt Lake City, UT;2. Center For Human Toxicology, University of Utah, Salt Lake City, UT;3. Department of Pathology, University of Utah, Salt Lake City, UT;4. Department of Medical Toxicology, Banner Good Samaritan Medical Center, University of Arizona College of Medicine‐Phoenix, Phoenix, AZ;5. Department of Medicine and Center for Toxicology and Pharmacology Education and Research, University of Arizona College of Medicine‐Phoenix, Phoenix, AZ;6. Office of the Medical Examiner, Utah Department of Health, Salt Lake City, UT;7. Animal Reference Pathology, Division, ARUP Laboratories, Salt Lake City, UT |
| |
| 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. |
| |
| Keywords: | forensic science acetaminophen clinical laboratory techniques protein‐derived APAP‐CYS postmortem redistribution acetaminophen– protein adducts |
|
|
