A new pyrazole-carboxamide type synthetic cannabinoid AB-CHFUPYCA [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide] identified in illegal products

Uchiyama, Nahoko; Asakawa, Kazuhiro; Kikura‐Hanajiri, Ruri; Tsutsumi, Taizo; Hakamatsuka, Takashi

doi:10.1007/s11419-015-0283-8

Cited by 29 publications

(28 citation statements)

References 22 publications

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“…Many countries scheduled SC as illicit substances, but clandestine laboratories continue to produce new molecules to circumvent the law. In Japan, where the scheduling process is the fastest, 858 SC were controlled by April 2015 (6). As the occurrence of consumption and the diversity of SC increased, SC intake is associated with considerable morbidity and mortality (7)(8)(9)(10).…”

Section: Introductionmentioning

confidence: 99%

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

Carlier

Diao

Sempio

et al. 2017

AAPS J

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Abstract.ADB-CHMINACA (MAB-CHMINACA) is a new synthetic cannabinoid with high potency and many reported adverse events and fatalities. The drug is currently scheduled in several countries in Europe and the USA. Analytical methods need to be developed to confirm ADB-CHMINACA intake for clinical and forensic programs. For many synthetic cannabinoids, parent compound is not detectable in biological samples after intake, making the detection of metabolites the only way to prove consumption. Therefore, detection of ADB-CHMINACA metabolites in biological specimens is critical. Since there are currently no published data on ADB-CHMINACA metabolism, we aimed to identify its major metabolites. Cryopreserved human hepatocytes were incubated with 10 μmol/L ADB-CHMINACA for 3 h. Incubations were analyzed with liquid chromatography on a biphenyl column, high resolution tandem mass spectrometry (orbitrap), and metabolite identification software. A reference standard of six commercially available potential metabolites was simultaneously analyzed under the same conditions to allow correct assignment of isomers. We detected ten major metabolites. Biotransformations mainly occurred at the cyclohexylmethyl tail of the compound, as also observed with structural analogs' metabolism. Minor reactions also occurred at the tert-butyl chain. Only two analytical standards of potential metabolites matched an actual metabolite detected in hepatocyte incubations. We recommend A9 (ADB-CHMINACA hydroxycyclohexylmethyl), A4 (ADB-CHMINACA 4″-hydroxycyclohexyl), and A6 (ADB-CHMINACA hydroxycyclohexylmethyl) as metabolite targets to document ADB-CHMINACA intake in clinical and forensic cases. Additionally, these results will guide analytical standard manufacturers to better provide suitable references for further studies on ADB-CHMINACA metabolism.

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Section: Introductionmentioning

confidence: 99%

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

Carlier

Diao

Sempio

et al. 2017

AAPS J

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“…A total of 858 SC were scheduled in Japan as narcotics or designated substances as of April 2015 (9). Despite regulations, clandestine laboratories continuously produce structurally diverse compounds to circumvent scheduling legislation.…”

Section: Introductionmentioning

confidence: 99%

In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22

Diao

Scheidweiler

Wohlfarth

et al. 2016

AAPS J

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Abstract. In 2014, FDU-PB-22 and FUB-PB-22, two novel synthetic cannabinoids, were detected in herbal blends in Japan, Russia, and Germany and were quickly added to their scheduled drugs list. Unfortunately, no human metabolism data are currently available, making it challenging to confirm their intake. The present study aims to identify appropriate analytical markers by investigating FDU-PB-22 and FUB-PB-22 metabolism in human hepatocytes and confirm the results in authentic urine specimens. For metabolic stability, 1 μM FDU-PB-22 and FUB-PB-22 was incubated with human liver microsomes for up to 1 h; for metabolite profiling, 10 μM was incubated with human hepatocytes for 3 h. Two authentic urine specimens from FDU-PB-22 and FUB-PB-22 positive cases were analyzed after β-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was accomplished by high-resolution mass spectrometry using information-dependent acquisition. Both FDU-PB-22 and FUB-PB-22 were rapidly metabolized in HLM with half-lives of 12.4 and 11.5 min, respectively. In human hepatocyte samples, we identified seven metabolites for both compounds, generated by ester hydrolysis and further hydroxylation and/or glucuronidation. After ester hydrolysis, FDU-PB-22 and FUB-PB-22 yielded the same metabolite M7, fluorobenzylindole-3-carboxylic acid (FBI-COOH). M7 and M6 (hydroxylated FBI-COOH) were the major metabolites. In authentic urine specimens after β-glucuronidase hydrolysis, M6 and M7 also were the predominant metabolites. Based on our study, we recommend M6 (hydroxylated FBI-COOH) and M7 (FBI-COOH) as suitable urinary markers for documenting FDU-PB-22 and/or FUB-PB-22 intake.

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“…A total of 858 SCs were scheduled in Japan as narcotics or designated substances as of April 2015 [13]. Besides structural analogs, a new trend is forming, namely positional isomers are now appearing on the illegal drug market.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo human metabolism of a new synthetic cannabinoid NM-2201 (CBL-2201)

et al. 2016

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In 2014, NM-2201 (CBL-2201), a novel synthetic cannabinoid (SC), was detected by Russian and United States laboratories. It was already added to the scheduled drugs list in Japan, Sweden and Germany. Unfortunately, no human metabolism data are currently available, making it challenging to confirm its intake because all previous investigated SCs were extensively metabolized. The present study aims to recommend appropriate marker metabolites by investigating NM-2201 metabolism in human hepatocytes and confirm the results in authentic human urine specimens. For the metabolic stability assay, 1 μM NM-2201 was incubated in human liver microsomes (HLMs) for up to 1 h; for metabolite profiling, 10 μM of NM-2201 was incubated in human hepatocytes for 3 h. Two authentic urine specimens from NM-2201 positive cases were analyzed after β-glucuronidase hydrolysis. Metabolite identification in hepatocyte samples and urine specimens was achieved with high-resolution mass spectrometry via information-dependent acquisition. NM-2201 was quickly metabolized in HLMs with an 8.0 min half-life. In human hepatocyte incubation samples, a total of thirteen NM-2201 metabolites were identified, generated mainly from ester hydrolysis and further hydroxylation, oxidative defluorination and subsequent glucuronidation. M13 (5-fluoro PB-22 3-carboxyindole) was the major metabolite. In the urine specimens, the parent drug NM-2201 was not detected; M13 was the predominant metabolite after β-glucuronidase hydrolysis. Therefore, based on our study, we recommend the M13 as a suitable urinary marker metabolite for confirming NM-2201 and/or 5F-PB-22 intake.

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A new pyrazole-carboxamide type synthetic cannabinoid AB-CHFUPYCA [N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(cyclohexylmethyl)-3-(4-fluorophenyl)-1H-pyrazole-5-carboxamide] identified in illegal products

Cited by 29 publications

References 22 publications

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

Identification of New Synthetic Cannabinoid ADB-CHMINACA (MAB-CHMINACA) Metabolites in Human Hepatocytes

In Vitro and In Vivo Human Metabolism of Synthetic Cannabinoids FDU-PB-22 and FUB-PB-22

In vitro and in vivo human metabolism of a new synthetic cannabinoid NM-2201 (CBL-2201)

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