heroin and norfentanyl

The USA and numerous other countries worldwide are currently experiencing a public health crisis due to the abuse of heroin and illicitly manufactured fentanyl. We have developed a liquid chromatography tandem mass spectrometry (LC-MS-MS)-based method for the detection of morphine, fentanyl and their metabolites, including morphine-3-glucuronide (M3G), morphine-6-glucuronide (M6G), normorphine, norfentanyl and deuterated internal standards in limited sample volumes with the limit of detection of 5.0/0.5 ng/mL (morphine, M3G, M6G, normorphine/fentanyl, norfentanyl). The inter-assay precision (%CV) was less than 12% for all assays, and the inter-assay bias (%) was less than 5%. The ruggedness of the method, dilution effect and carryover were also investigated as part of the study. The simultaneous quantification of morphine, fentanyl and its metabolites via this simple and time- and cost-efficient method could be successfully applied to samples taken for pharmacokinetic evaluation (antemortem and postmortem) after a single dose of morphine or co-administration of morphine with other drugs (e.g., fentanyl) in rats.

Topics: Animals; Chromatography, Liquid; Fentanyl; Heroin; Morphine; Morphine Derivatives; Rats; Reproducibility of Results; Substance Abuse Detection; Tandem Mass Spectrometry

Acetyl fentanyl (N-[1-phenethylpiperidin-4-yl]-N-phenylacetamide) is a potent opioid analgesic with no medicinal uses. We report deaths between 2016 and 2017 at the Medical Examiner's Office in Detroit, MI where acetyl fentanyl was found in the decedent's blood and compare them to previously published deaths between 2015 and 2016. The recent cases (cohort B) had a mean acetyl fentanyl concentration of 0.9 ng/mL (range: 0.1-5.3 ng/mL) and an associated higher concentration of fentanyl along with multiple other drugs present. The older cases (cohort A) had higher concentrations of acetyl fentanyl (mean: 8.9 ng/mL; range: 0.28-37 ng/mL) with lower, yet still toxic, concentrations of fentanyl. We conclude that the cause of death in these recent cases was likely multiple drug toxicity with fentanyl and that the consistently observed lower peripheral blood concentrations of acetyl fentanyl are most likely an artifact in the manufacture of the consumed illicit fentanyl.

Topics: Adult; Analgesics, Opioid; Benzodiazepines; Central Nervous System Depressants; Chromatography, Liquid; Cocaine; Cohort Studies; Coroners and Medical Examiners; Drug Overdose; Ethanol; Female; Fentanyl; Heroin; Humans; Illicit Drugs; Male; Mass Spectrometry; Michigan; Opioid-Related Disorders; Racial Groups; Urban Population