Assessment of postmortem urine fentanyl detection by autopsy dipstick testing in accidental overdose deaths.

Accidental overdose cases continue to rise due to the opioid epidemic in the USA, namely, the widespread availability and use of fentanyl. Medical examiners and coroners across the country have been subsequently burdened, and with limited resources, some seek alternative triaging processes to identify overdoses. Point-of-care urine dipstick testing at autopsy is one such idea that may be used in various ways to instigate or negate the need for an autopsy or regular forensic toxicology laboratory testing. This study investigated the frequency and estimated quantitative fentanyl and norfentanyl concentrations in the postmortem urine of fentanyl-related accidental overdose deaths, as well as the effectiveness of commercially available point-of-care urine dipstick tests based on such concentrations. A total of 1550 fentanyl-related accidental overdose cases, where both the postmortem peripheral femoral blood and urine were tested, were reviewed. Of these, using sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) laboratory testing, 82 cases (5%) had a positive fentanyl or norfentanyl detection in the blood, while fentanyl or norfentanyl remained undetected in the urine. Furthermore, a comparison of commercially available urine dipstick test cut-offs and authentic casework with estimated urine concentrations revealed that at a fentanyl/norfentanyl cut-off level of 5 ng/mL, 19% of these fentanyl-related accidental overdoses would result in a false negative, 24% at 10 ng/mL, 25% at 20 ng/mL, 51% at 50 ng/mL, and 61% at 100 ng/mL. The study found that the use of urine dipstick tests, as a decision-maker for the initiation of further comprehensive routine toxicology laboratory testing, or to support cause and manner of death determination, leads to both false-positive and false-negative predictions in fentanyl accidental overdoses.

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.

Electrochemical oxidative rearrangement of tetrahydro-ß-carbolines in a zero-gap flow cell.

Oxidative rearrangement of tetrahydro-ß-carbolines (THßCs) is one of the most efficient methods for the synthesis of biologically active spirooxindoles, including natural products and drug molecules. Here, we report the first electrochemical approach to achieve this important organic transformation in a flow cell. The key to the high efficiency was the use of a multifunctional LiBr electrolyte, where the bromide (Br-) ion acts as a mediator and catalyst and lithium ion (Li+) acts as a likely hydrophilic spectator, which might considerably reduce diffusion of THßCs into the double layer and thus prevent possible nonselective electrode oxidation of indoles. Additionally, we build a zero-gap flow cell to speed up mass transport and minimize concentration polarization, simultaneously achieving a high faradaic efficiency (FE) of 96% and an outstanding productivity of 0.144 mmol (h-1 cm-2). This electrochemical method is demonstrated with twenty substrates, offering a general, green path towards bioactive spirooxindoles without using hazardous oxidants.