Trace residue identification, characterization, and longitudinal monitoring of the novel synthetic opioid β‐U10, from discarded drug paraphernalia

Abstract

Empirical data regarding dynamic alterations in illicit drug supply markets in response to the COVID‐19 pandemic, including the potential for introduction of novel drug substances and/or increased poly‐drug combination use at the “street” level, that is, directly proximal to the point of consumption, are currently lacking. Here, a high‐throughput strategy employing ambient ionization‐mass spectrometry is described for the trace residue identification, characterization, and longitudinal monitoring of illicit drug substances found within >6,600 discarded drug paraphernalia (DDP) samples collected during a pilot study of an early warning system for illicit drug use in Melbourne, Australia from August 2020 to February 2021, while significant COVID‐19 lockdown conditions were imposed. The utility of this approach is demonstrated for the de novo identification and structural characterization of β‐U10, a previously unreported naphthamide analog within the “U‐series” of synthetic opioid drugs, including differentiation from its α‐U10 isomer without need for sample preparation or chromatographic separation prior to analysis. Notably, β‐U10 was observed with 23 other drug substances, most commonly in temporally distinct clusters with heroin, etizolam, and diphenhydramine, and in a total of 182 different poly‐drug combinations. Longitudinal monitoring of the number and weekly “average signal intensity” (ASI) values of identified substances, developed here as a semi‐quantitative proxy indicator of changes in availability, relative purity and compositions of street level drug samples, revealed that increases in the number of identifications and ASI for β‐U10 and etizolam coincided with a 50% decrease in the number of positive detections and an order of magnitude decrease in the ASI for heroin.

In vitro μ‐opioid receptor activation potential of U10 and β‐U10, positional isomers of the synthetic opioid naphthyl U‐47700

“…β‐U10 has been identified in drug material 11,14 and discarded drug paraphernalia 12 in Australia and the United States, commonly alongside heroin and designer benzodiazepines. Notably, β‐U10 has only been identified in the absence of U10.…”

“…Considering the higher MOR activation potential of β‐U10 compared with U10, it is not surprising that β‐U10 may prevail over U10 on the NSO market. Full chemical characterization of both regioisomers has been previously reported 11,12,15,17 …”

“…In the second half of 2020, “β‐U10” (2‐naphthyl U‐47700 or N ‐[2‐(dimethylamino)cyclohexyl]‐ N ‐methylnaphthalene‐2‐carboxamide) (Figure 1) was identified in a seized powder 11 and in discarded drug paraphernalia 12 in Australia. This compound, a close bioisosteric analogue of U‐47700 originating from an Upjohn patent, 13 had not been encountered before in a recreational drug context.…”

A snapshot of injecting drug consumption from the analysis of used syringes within the Medically Supervised Injecting Centre in Sydney, Australia

“…The analysis of used injecting paraphernalia has been accomplished in a variety of locations in Europe [16,18], the United States of America [19] and Australia [20,21]. Analysis of used injecting paraphernalia has provided valuable insights into adulteration and emerging drug trends at the consumption level, such as further examining the growing fentanyl-laced opioid epidemic in the United States [22] and other new psychoactive substances emergence [19].…”

“…In Washington, DC, a high prevalence of fentanyl polydrug mixtures was detected in heroin (60% of heroin specimens), tramadol (88% of tramadol specimens) and cocaine (61% of cocaine specimens) [19]. Used injecting paraphernalia analysis completed in Victoria, Australia, after the onset of COVID-19 detected a relatively high prevalence of β-U10 and etizolam, both of which are highly potent new psychoactive substances that present a significant public health risk [21].…”