Identification of a thermal degradation product of CUMYL‐PEGACLONE and its detection in biological samples

Abstract

The structural diversity of synthetic cannabinoids makes it a challenging task to have a comprehensive screening method for this class of drugs. The difficulty is increased by the fact that some synthetic cannabinoids undergo thermal decomposition during common routes of administration, such as smoking or vaping. CUMYL‐PEGACLONE is a relatively new synthetic cannabinoid which has a structural variant from most other synthetic cannabinoids: a γ‐carbolinone core. To investigate its thermal stability, CUMYL‐PEGACLONE was heated in an oven at temperatures ranging from 200 to 350oC, and a major thermal degradation product, N‐pentyl‐γ‐carbolinone, was subsequently identified. Unlike some other synthetic cannabinoids, the thermal degradation product of CUMYL‐PEGACLONE is not one of its known metabolites, nor were any known metabolites detected during the thermal stability experiments. The degradation product was formed in significant amounts at temperatures above 250°C, and has been detected (along with CUMYL‐PEGACLONE) in case samples, including post‐mortem blood and urine, and residue found at a scene.

Adding more “spice” to the pot: A review of the chemistry and pharmacology of newly emerging heterocyclic synthetic cannabinoid receptor agonists

“…5F‐AB‐PINACA ( 80 ) and 5F‐AMB ( 81 ) are both examples of indazole SCRAs which bear a 5‐ fluoropentyl “tail group”. N ‐ n ‐Pentyl‐γ‐carbolinone ( 84 ) is the major thermal degradant of CUMYL‐PEGACLONE ( 63 )…”

“…The preservation of the terminal fluorine atom in metabolite 83 , supports its utility as a specific metabolite marker for the consumption of 64 . Nash et al have recently investigated the thermal degradation (200–350°C) of 63 and demonstrated that the major degradant formed under such conditions is N ‐ n ‐pentyl‐γ‐carbolinone ( 84 ) . Importantly, the authors caution that the latter study may not provide an accurate thermal degradation profile of 63 , as the temperature distribution within a traditional cigarette (~ 900°C) or “e‐cigarette” (40–950°C) can vary significantly.…”

“…Importantly, the authors caution that the latter study may not provide an accurate thermal degradation profile of 63 , as the temperature distribution within a traditional cigarette (~ 900°C) or “e‐cigarette” (40–950°C) can vary significantly. Nonetheless, the thermal degradation product, N ‐ n ‐pentyl‐γ‐carbolinone, has been detected in seven recent post‐mortem samples (blood and/or urine) …”

Air monitoring for illegal drugs including new psychoactive substances: A review of trends, techniques and thermal degradation products

“…28,88,94 Drug thermal degradation experiments will need to consider the desired temperature range for the work; a suitable temperature range reflects the drug paraphernalia that drug users utilise which may range between: cigarettes, electronic cigarettes (E-cigs), aluminium foil, glass pipe/surface or a tube furnace. Different paraphernalia reach different temperatures; smoking for example (with a cigarette typically) can reach high temperatures up to 700-900 C and there are some toxic breakdown products that are not produced until approximately 200 C. 94,96 An 'e-cig' can have a very large temperature range; Chen et al 97 investigated the heating coil temperature for e-cigarettes under different conditions (dry, wet-through-wick and full-wet) and found that it could range from 40-950 C. Other miscellaneous paraphernalia used for heating such as a glass bulb was found to reach over 300 C when heated with a disposable lighter to heat a powder until it turned to tar. 27 Various studies have examined the temperature range for these different paraphernalia, as well as the 'optimal' temperature for an efficient combustion/heating of the product; for example, Nakahara et al 85 investigated the pyrolysis of crack and cocaine hydrochloride and their degradation products produced at different temperatures.…”

Structural confirmation of synthetic cannabinoids in seized electronic cigarette oil: A combined mass spectrometric and computational study

“…Lacking in relevant structural data on these new substances, it is difficult to detect and monitor them in drug laboratories. 6 Although nuclear magnetic resonance spectroscopy shows substantial advantages in structural identification, it requires high sample purity and quantity, being difficult to effectively identify new psychoactive substances in mixtures. 7 However, with the strong separation performance and characterization of chromatography combined with mass spectrometry (MS), rich structural information on unknown substances can be obtained through multi-stage MS analysis.…”