Fluorofentanyl and Novel Synthetic Opioids in Accidental Overdose Deaths.

One of the quickest-growing subclasses of novel psychoactive substances is novel synthetic opioids (NSO), which are categorized as fentanyl analogs (fentalogs) or non-fentanyl opioids that bind to the mu-opioid receptor. Increased detections of NSO have been observed in the United States. However, limited information on their prevalence outside of the East Coast is available. This study details the prevalence of NSO, specifically fluorofentanyl, in the biological and drug paraphernalia specimens of accidental overdose deaths in San Francisco in 2022. A recently developed and validated LC-MS-MS method was utilized for the analysis of over 250 NSO. Out of the 649 accidental overdose deaths in 2022, 617 cases were available for blood analysis, with at least one NSO detected in 48 cases (7.8%). Fentalogs were detected in all 48 cases, with fluorofentanyl being detected in 40 cases. In postmortem femoral blood, estimated concentrations of fluorofentanyl ranged from 0.1 to 8.9 ng/mL, and 0.05 to 85 ng/mL in urine. Polysubstance use with NSO was seen with fentanyl (89.6%), methamphetamine (70.8%), cocaine (33.3%), and heroin (18.8%). NSO, mainly, fluorofentanyl were observed in matched drug paraphernalia. This report documents the migration of fluorofentanyl to the West Coast, specifically California.

Analysis of over 250 novel synthetic opioids and xylazine by LC-MS-MS in blood and urine.

Novel Synthetic Opioids (NSO) are frequently found in postmortem (PM) and human performance (HP) forensic toxicology casework, resulting in impairment and fatal overdoses. Developing a broad NSO method benefits public health, as it can be used to identify trends in potent opioid use to develop risk management programs. This project aimed to design a comprehensive, rapid and routine method for the selective analysis of over 250 novel synthetic opioids in blood and urine. This method rapidly extracted 150 µL of blood or urine via protein precipitation followed by size-exclusion filtration, evaporation and reconstitution. Separation and data acquisition were achieved on a 12 min LC-MS-MS method using an F5 column. Data processing was expedited with a custom built-in query created in-house that automated processing and enhanced quality assurance. Validation according to ASB/ANSI Standard 036 was performed and applicability of the method was assessed using proficiency test and authentic casework samples. Assessed in blood and urine qualitatively were 261 unique analytes including fentanyl analogs (fentalogs), nitazenes and other miscellaneous synthetic opioids. As 59 isomeric target analytes were placed into groups due to co-elution, there were 202 distinct acquired targets or target - groups. To demonstrate applicability, 27 proficiency test blood samples received over an approximate 4-year period were analyzed with 126 expected results assessed comprising 25 unique target analytes. Additionally, 617 fatal accidental overdoses within San Francisco in 2022 were retroactively analyzed by this method with almost 10% of cases containing a new NSO substance(s). Such trends and NSO substances were previously unknown in this community.