Human urinary metabolite pattern of a new synthetic cannabimimetic, methyl 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoate
A number of metabolites of a new synthetic cannabimimetic, which is a derivative of 2-(1-(cyclohexylmethyl)-1H-indole-3-carboxamido)-3,3-dimethylbutanoic acid, were identified in human urine. The parent compound, a methyl ester of this acid, was identified in seizures in persons from the same city where analysis of drug-intoxication urine samples revealed the presence of the compound’s metabolites. This compound named ‘MDMB-CHMICA’ was reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) via the Early Warning System (EWS) in 2014. Hydrolysis of the ester was found to be the main metabolic pathway followed by mono-, di- and tri-hydroxylation, ketone formation, ketone formation with monohydroxylation, dealkylation, and dealkylation combined with hydroxylation. Additionally, the products by internal dehydration of hydroxylated forms with lactone formation were detected. Mono-hydroxylated metabolites were detected from their glucuronidated forms. Identification of metabolites was made on the basis of gas chromatography–mass spectrometry and liquid chromatography with time-of-flight mass spectrometry and ion trap mass spectrometry. To our knowledge, this is the first report on the metabolites of MBDB-CHMICA in human urine.
KeywordsSynthetic cannabinoid MDMB-CHMICA Human urine Metabolites GC–MS LC–QTOF LC–MSn
Compliance with ethical standards
Conflict of interest
There are no financial or other relations that could lead to a conflict of interest.
Statement of human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
For this type of study formal consent is not required.
- 1.EMCDDA (2015) European drug report 2015: trends and developments, 2015. http://www.emcdda.europa.eu/attachements.cfm/att_239505_EN_TDAT15001ENN.pdf. Accessed Feb 2016
- 2.EMCDDA (2009) Thematic papers. Understanding the ‘Spice’ phenomenon. http://www.emcdda.europa.eu/attachements.cfm/att_80086_EN_Spice%20Thematic%20paper%20%E2%80%94%20final%20version.pdf. Accessed Feb 2016
- 3.Reggio PH (ed) (2009) The cannabinoid receptors. Humana Press, New York CityGoogle Scholar
- 8.Hasegawa K, Wurita A, Minakata K, Gonmori K, Yamagishi I, Nozawa H, Watanabe K, Suzuki O (2015) Identification and quantitation of 5-fluoro-ADB, one of the most dangerous synthetic cannabinoids, in the stomach contents and solid tissues of a human cadaver and in some herbal products. Forensic Toxicol 33:112–121CrossRefGoogle Scholar
- 12.Shevyrin V, Melkozerov V, Nevero A, Eltsov O, Baranovsky A, Shafran Y (2014) Synthetic cannabinoids as designer drugs: new representatives of indol-3-carboxylates series and indazole-3-carboxylates as novel group of cannabinoids. Identification and analytical data. Forensic Sci Int 244:263–275CrossRefPubMedGoogle Scholar
- 14.Uchiyama N, Matsuda S, Wakana D, Kikura-Hanajiri R, Goda Y (2013) New cannabimimetic indazole derivatives, N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-pentyl-1H-indazole-3-carboxamide (AB-PINACA) and N-(1-amino-3-methyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1H-indazole-3-carboxamide (AB-FUBINACA) identified as designer drugs in illegal product. Forensic Toxicol 31:93–100CrossRefGoogle Scholar
- 15.Uchiyama N, Shimokawa Y, Kawamura M, Kikura-Hanajiri R, Hakamatsuka T (2014) Chemical analysis of a benzofuran derivative, 2-(2-ethylaminopropyl) benzofuran (2-EAPB), eight synthetic cannabinoids, five cathinone derivatives, and five other designer drugs newly detected in illegal products. Forensic Toxicol 32:266–281CrossRefGoogle Scholar
- 18.Hasegawa K, Wurita A, Minakata K, Gonmori K, Nozawa H, Yamagishi I, Watanabe K, Suzuki O (2015) Postmortem distribution of AB-CHMINACA, 5-fluoro-AMB, and diphenidine in body fluids and solid tissues in a fatal poisoning case: usefulness of adipose tissue for detection of the drugs in unchanged forms. Forensic Toxicol 33:45–53CrossRefGoogle Scholar
- 23.Wohlfarth A, Castaneto MS, Zhu M, Pang S, Scheidweiler KB, Kronstrand R, Huestis MA (2015) Pentylindole/pentylindazole synthetic cannabinoids and their 5-fluoro analogs produce different primary metabolites: metabolite profiling for AB-PINACA and 5F-AB-PINACA. AAPS J 17:660–667CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Vikingsson S, Gréen H, Brinkhagen L, Mukhtar S, Josefsson M (2015) Identification of AB-FUBINACA metabolites in authentic urine samples suitable as urinary markers of drug intake using liquid chromatography quadrupole tandem time of flight mass spectrometry. Drug Test Anal. doi: 10.1002/dta.1896 PubMedGoogle Scholar
- 30.Bruker Daltonics (2012) Toxtyper™. https://www.bruker.com/products/mass-spectrometry-and-separations/lc-ms/ion-trap/toxtyper/overview.html. Accessed Feb 2016
- 31.Federal service for intellectual property (2015) MS Library ‘EKBDRUGS’. Certificate of registration RU 2015621086. http://www1.fips.ru/fips_servl/fips_servlet?DB=DB&rn=6957&DocNumber=2015621086&TypeFile=html. Accessed Jan 2016
- 32.EMCDDA (2014) EMCDDA–Europol 2014 annual report on the implementation of Council Decision 2005/387/JHA. http://www.emcdda.europa.eu/system/files/publications/1018/TDAN15001ENN.pdf. Accessed Feb 2016