Metonitazene in the United States—Forensic toxicology assessment of a potent new synthetic opioid using liquid chromatography mass spectrometry

• Published in: Drug testing and analysis Vol. 13; no. 10; pp. 1697 - 1711
• Main Authors: Krotulski, Alex J., Papsun, Donna M., Walton, Sara E., Logan, Barry K.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-10-2021
• Subjects: Adult; Analgesics, Opioid - analysis; Autopsy; Chromatography; Chromatography, Liquid - methods; Female; Fentanyl - analysis; forensic; Forensic Toxicology - methods; Humans; Illicit Drugs - analysis; LC‐MS; Male; Mass spectrometry; Mass Spectrometry - methods; Methadone; Middle Aged; Narcotics; NPS; opioid; Recreational drugs; Scientific imaging; Substance Abuse Detection - methods; Toxicology; United States; United States; United States > US; NPS; toxicology; LC-MS; forensic; opioid
• ISSN: 1942-7603; 1942-7611
• DOI: 10.1002/dta.3115

Metonitazene is considered a new psychoactive substance (NPS) and emerging potent synthetic opioid, causing increased public health concern beginning in 2020. Metonitazene joins a growing list of new synthetic opioids (NSOs) contributing to deaths among people who use drugs in the United States and other parts of the world. Metonitazene (a 2‐benzylbenzimidazole analogue) first appeared in mid‐2020 in the recreational drug supply and subsequently began proliferating in death investigation casework towards the end of 2020. Screening and metabolite discovery were performed by liquid chromatography quadrupole time‐of‐flight mass spectrometry. Quantitative confirmation was performed by liquid chromatography tandem quadrupole mass spectrometry. Metonitazene was confirmed in 20 authentic forensic postmortem cases with an average concentration in blood at 6.3 ± 7.5 ng/ml (median: 3.8 ng/ml, range: 0.5–33 ng/ml, n = 18) and in urine at 15 ± 13 ng/ml (median: 11 ng/ml, range: 0.6–46 ng/ml, n = 14). Metonitazene was the only opioid identified in 30% of cases but was also found in combination with fentanyl (55%) and NPS benzodiazepines, opioids, and hallucinogens (45%). Medical examiners included metonitazene as a drug responsible for the cause of death, and the manner of death was always ruled to be an accident. The metabolism of metonitazene was found to be similar to that of isotonitazene, a closely related analogue. Toxicology laboratories and death investigators should ensure that metonitazene is included in forensic testing protocols, all while remaining vigilant for subsequent NSOs to emerge.
Metonitazene is considered a new psychoactive substance (NPS) of the new synthetic opioid subclass. Metonitazene is a potent opioid and the latest of which to emerge in the recreational drug supply. A comprehensive toxicology assessment was conducted for this drug, including quantitative confirmations, assessment of poly‐drug use, metabolite profiling, and inclusion of detailed case histories and autopsy findings. Metonitazene was listed as a cause of death in 3 cases (manner of death: accident), demonstrating the toxicity of this new opioid.