Gas and Liquid Chromatography-Mass Spectrometry Detection of the Urinary Metabolites of UR-144 and Its Major Pyrolysis Product

Abstract

Studies on the pyrolysis of the synthetic cannabinoid agonist UR-144 ((1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone) have shown that its major pyrolysis product is a tetramethylcyclopropane ring-opened alkene. Considering that smoking is a common way of ingesting synthetic cannabimimetics, the presence of the metabolites of this pyrolysis product would be expected in biological fluids. Using GC-MS and LC-MS-MS methods, a series of phase I metabolites of UR-144 and its pyrolysis product were detected in the urine samples from patients admitted to hospital with suspected drug intoxication. The metabolites were tentatively identified as the products of mono-hydroxylation, di-hydroxylation, mono-hydroxylation with formation of the carbonyl group on the N-alkyl chain, carboxylation and N-dealkylation with mono-hydroxylation. In the case of the UR-144 pyrolysis product, metabolites with hydration of the aliphatic double bond were also identified. The parent compounds were detected as trace amounts in some urine samples, and the hydrated derivative of the UR-144 pyrolysis product was detected in the majority of samples. The detection of mono-hydroxylated metabolites of UR-144 (LC-MS-MS) and mono-hydroxylated/with hydration metabolites of the UR-144 pyrolysis product (GC-MS) was found to be the most useful method of establishing UR-144 ingestion.

New challenges in toxicology of new psychoactive substances exemplified by fatal cases after UR-144 and UR-144 with pentedrone administration determined by LC-ESI-MS-MS in blood samples

“…Archiwum Medycyny Sądowej i Kryminologii Archives of Forensic Medicine and Criminology Z nielicznych prac eksperymentalnych [15][16][17] wynika, że metabolizm UR-144 przebiega poprzez hydroksylację i dalsze sprzęganie z kwasem glukuronowym i siarkowym, inne drogi metaboliczne obejmują m.in. dehydratację, hydroksylację, dealkilację, karboksylację.…”

“…Grigoryev i wsp. [16] określili w toku swoich badań w moczu pacjentów z podejrzeniem zatrucia UR-144 ponad 16 metabolitów oraz 21 produktów pyrolizy. Dane z piśmiennictwa wskazują, że syntetyczne kannabinoidy podlegają intensywnym procesom metabolicznym, macierzyste substancje rzadko są identyfikowane we krwi, ślinie, włosach czy moczu lub ich stężenia są niskie.…”

“…Podobieństwo w mechanizmie działania poszczególnych syntetycznych kannabinoidów sprawia, że istnieje również podobieństwo w efektach działania między UR-144 a JWH-122 i AM-2201 czy marihuaną. Obejmują one takie odScarce experimental studies [15][16][17] demonstrate that UR-144 is metabolized by hydroxylation and further conjugation with glucuronic and sulphuric acids. Other metabolic routes include dehydration, hydoxylation, dealkylation and carboxylation.…”

“…Other metabolic routes include dehydration, hydoxylation, dealkylation and carboxylation. Grigoryev et al [16] detected over 16 metabolites and 21 pyrolysis products in the urine of patients suspected of UR-144 poisoning. The literature data indicate that synthetic cannabinoids are intensively metabolized, and parent substances are rarely detectable in the blood, saliva, hair or urine, or their identified concentrations are low.…”

Bioanalytical methods for the determination of synthetic cannabinoids and metabolites in biological specimens

“…Another example is that cyclopropyl (e.g. UR-144) undergoes a thermal degradation (isomerization) mainly in GC column [108,109]. This is indicated by shape of chromatographic peaks and variation of GC conditions.…”