Fatality Following Ingestion of Tetrahydrofuranylfentanyl, U-49900 and Methoxy-Phencyclidine

Novel psychoactive substances (NPS), and specifically novel opioids, continue to cause adverse events, including death, within drug-using populations. As the number of opioid-related overdoses continues to increase, laboratories have identified the emergence of new fentanyl analogues and other synthetic opioid-related drugs. Tetrahydrofuranylfentanyl (THFF) has been identified in Europe and the United States as an emerging novel opioid, causing death in at least 15 drug-using individuals to date. THFF is structurally similar to furanylfentanyl, a previously characterized novel opioid responsible for numerous adverse events, including death. In this case report, THFF, U-49900 and methoxy-phencyclidine were identified in postmortem blood and urine specimens collected after a suspected overdose. As part of the death investigation, an unknown substance was collected from the scene and analytically confirmed as THFF and U-49900. To further assist laboratories in identifying THFF ingestion, metabolic profiling was conducted using pooled human liver microsomes. Characterized metabolites were then confirmed in the specimens collected during this investigation. In total, seven metabolites were identified for THFF, most notably THF-norfentanyl and hydroxyl-THFF. THF-norfentanyl provides utility as a biomarker because it is a unique metabolite of THFF. 4-Anilino-N-phenethylpiperidine (4-ANPP) and its metabolite, hydroxyl-4-ANPP, were identified in microsomal incubations and collected specimens, but usefulness as biomarkers is limited due to commonality between other fentanyl analogues and co-ingestion as a synthesis precursor. To our knowledge, this case report is the first to document a fatality after ingestion of THFF and U-49900 in the United States.