Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids

Drug Testing and Analysis

Volumn 4, Issue 10, 2012, Pages 745-753

  Sobolevsky, Tim ^a   Prasolov, Ilya ^a   Rodchenkov, Grigory ^a  

^a Moscow Antidoping Centre   (Russian Federation)

Author keywords

AM 2201; Anti doping analysis; KM X1; Synthetic cannabinoids; UR 144

Indexed keywords

BIODEGRADATION; BIOMOLECULES; DRUG PRODUCTS; ELECTROSPRAY IONIZATION; HYDROXYLATION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLISM;

AM-2201; ANTI-DOPING ANALYSE; DOPING ANALYSIS; HUMAN LIVER MICROSOMES; IN-VITRO; KM-X1; METHANONE; SYNTHETIC CANNABINOID; UR-144; URINARY METABOLITES;

METABOLITES;

(1-PENTYL-1H-INDOL-3-YL)(2,2,3,3-TETRAMETHYLCYCLOPROPYL)METHANONE; 1-((5-FLUOROPENTYL)-1H-INDOL-3-YL)-(NAPHTHALEN-1-YL)METHANONE; CANNABINOID; INDOLE DERIVATIVE; NAPHTHALENE DERIVATIVE; STREET DRUG;

CHEMISTRY; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; LIVER MICROSOME; MASS FRAGMENTOGRAPHY; METABOLISM; SUBSTANCE ABUSE; TANDEM MASS SPECTROMETRY; URINE;

CANNABINOIDS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HUMANS; INDOLES; MICROSOMES, LIVER; NAPHTHALENES; STREET DRUGS; SUBSTANCE ABUSE DETECTION; TANDEM MASS SPECTROMETRY;

EID: 84868194464     PISSN: 19427603     EISSN: 19427611     Source Type: Journal    
DOI: 10.1002/dta.1418     Document Type: Article

References (46)

1. S. Dresen, N. Ferreirós, M. Pütz, F. Westphal, R. Zimmermann, V. Auwärter. Monitoring of herbal mixtures potentially containing synthetic cannabinoids as psychoactive compounds. J. Mass Spectrom. 2010, 45, 1186.
2. S. Hudson, J. Ramsey, L. King, S. Timbers, S. Maynard, P.I. Dargan, et al. Use of high-resolution accurate mass spectrometry to detect reported and previously unreported cannabinomimetics in "herbal high" products. J. Anal. Toxicol. 2010, 34, 252.
3. J. Nakajima, M. Takahashi, T. Seto, C. Kanai, J. Suzuki, M. Yoshida, et al. Identification and quantitation of two benzoylindoles AM-694 and (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone, and three cannabimimetic naphthoylindoles JWH-210, JWH-122, and JWH-019 as adulterants in illegal products obtained via the internet. Forensic Toxicol. 2011, 29, 95.
4. P. Jankovics, A. Váradi, L. Tölgyesi, S. Lohner, J. Németh-Palotás, J. Balla. Detection and identification of the new potential synthetic cannabinoids 1-pentyl-3-(2-iodobenzoyl)indole and 1-pentyl-3-(1-adamantoyl)indole in seized bulk powders in Hungary. Forensic Sci. Int. 2012, 214, 27.
5. S. Kneisel, P. Bisel, V. Brecht, S. Broecker, M. Müller, V. Auwärter. Identification of the cannabimimetic AM-1220 and its azepane isomer (N-methylazepan-3-yl)-3-(1-naphthoyl)indole in a research chemical and several herbal mixtures. Forensic Toxicol. 2012, 30, 126.
6. B. Moosmann, S. Kneisel, U. Girreser, V. Brecht, F. Westphal, V. Auwärter. Separation and structural characterization of the synthetic cannabinoids JWH-412 and 1-[(5-fluoropentyl)-1H-indol-3yl]-(4-methylnaphthalen-1-yl)methanone using GC-MS, NMR analysis and a flash chromatography system. Forensic Sci. Int. 2012, 220, e17.
7. J. Nakajima, M. Takahashi, R. Nonaka, T. Seto, J. Suzuki, M. Yoshida, et al. Identification and quantitation of a benzoylindole (2-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone and a naphthoylindole 1-(5-fluoropentyl-1H-indol-3-yl)-(naphthalene-1-yl)methanone (AM-2201) found in illegal products obtained via the internet and their cannabimimetic effects evaluated by in vitro [35S]GTPγS binding assays. Forensic Toxicol. 2011, 29, 132.
8. J. Nakajima, M. Takahashi, T. Seto, M. Yoshida, C. Kanai, J. Suzuki, et al. Identification and quantitation of two new naphthoylindole drugs-of-abuse, (1-(5-hydroxypentyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone (AM-2202) and (1-(4-pentenyl)-1H-indol-3-yl)(naphthalen-1-yl)methanone, with other synthetic cannabinoids in unregulated "herbal" products circulated in the Tokyo area. Forensic Toxicol. 2012, 30, 33.
9. 2 receptors. Chem. Pharm. Bull. 2011, 59, 1203.
10. N. Uchiyama, M. Kawamura, R. Kikura-Hanajiri, Y. Goda. Identification of two new-type synthetic cannabinoids, N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (APINACA), and detection of five synthetic cannabinoids, AM-1220, AM-2233, AM-1241, CB-13 (CRA-13), and AM-1248, as designer drugs in illegal products. Forensic Toxicol. 2012, 30, 114.
11. N. Uchiyama, R. Kikura-Hanajiri, J. Ogata, Y. Goda. Chemical analysis of synthetic cannabinoids as designer drugs in herbal products. Forensic Sci. Int. 2010, 198, 31.
12. S. Hudson, J. Ramsey. The emergence and analysis of synthetic cannabinoids. Drug Test. Anal. 2011, 3, 466.
13. K.G. Shanks, T. Dahn, G. Behonick, A. Terrell. Analysis of first and second generation legal highs for synthetic cannabinoids and synthetic stimulants by ultra-performance liquid chromatography and time of flight mass spectrometry. J. Anal. Toxicol. 2012, 36, 360.
14. F. Westphal, F.D. Sönnichsen, S. Thiemt. Identification of 1-butyl-3-(1-(4-methyl)naphthoyl)indole in a herbal mixture. Forensic Sci. Int. 2012, 215, 8.
15. L. Ernst, H.M. Schiebel, C. Theuring, R. Lindigkeit, T. Beuerle. Identification and characterization of JWH-122 used as new ingredient in "spice-like" herbal incenses. Forensic Sci. Int. 2011, 208, 31.
16. M. Bononi, P. Belgi, F. Tateo. Analytical data for identification of the cannabimimetic phenylacetylindole JWH-203. J. Anal. Toxicol. 2011, 35, 360.
17. N. Uchiyama, M. Kawamura, R. Kikura-Hanajiri, Y. Goda. Identification and quantitation of two cannabimimetic phenylacetylindoles JWH-251 and JWH-250, and four cannabimimetic naphthoylindoles JWH-081, JWH-015, JWH-200, and JWH-073 as designer drugs in illegal products. Forensic Toxicol. 2011, 29, 25.
18. S. Kneisel, F. Westphal, P. Bisel, V. Brecht, S. Broecker, V. Auwärter. Identification and structural characterization of the synthetic cannabinoid 3-(1-adamantoyl)-1-pentylindole as an additive in "herbal incense". J. Mass Spectrom. 2012, 47, 195.
19. S. Dresen, S. Kneisel, W. Weinmann, R. Zimmermann, V. Auwärter. Development and validation of a liquid chromatography-tandem mass spectrometry method for the quantitation of synthetic cannabinoids of the aminoalkylindole type and methanandamide in serum and its application to forensic samples. J. Mass Spectrom. 2011, 46, 163.
20. A. Thomas, H. Geyer, S. Guddat, W. Schänzer, M. Thevis. Dried blood spots (DBS) for doping control analysis. Drug Test. Anal. 2011, 3, 806.
21. J. Teske, J.P. Weller, A. Fieguth, T. Rothämel, Y. Schulz, H.D. Tröger. Sensitive and rapid quantification of the cannabinoid receptor agonist naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018) in human serum by liquid chromatography-tandem mass spectrometry. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2010, 878, 2659.
22. J. Ammann, J.M. McLaren, D. Gerostamoulos, J. Beyer. Detection and quantification of new designer drugs in human blood: part 1 - synthetic cannabinoids. J. Anal. Toxicol. 2012, 36(6), 372.
23. S.L. Kacinko, A. Xu, J.W. Homan, M.M. McMullin, D.M. Warrington, B.K. Logan. Development and validation of a liquid chromatography-tandem mass spectrometry method for the identification and quantification of JWH-018, JWH-073, JWH-019, and JWH-250 in human whole blood. J. Anal. Toxicol. 2011, 35, 386.
24. C. Coulter, M. Garnier, C. Moore. Synthetic Cannabinoids in Oral Fluid. J. Anal. Toxicol. 2011, 35, 424.
25. T. Sobolevsky, I. Prasolov, G. Rodchenkov. Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Sci. Int. 2010, 200, 141.
26. I. Möller, A. Wintermeyer, K. Bender, M. Jübner, A. Thomas, O. Krug, et al. Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test. Anal. 2011, 3, 609.
27. S. Beuck, I. Möller, A. Thomas, A. Klose, N. Schlörer, W. Schänzer, et al. Structure characterisation of urinary metabolites of the cannabimimetic JWH-018 using chemically synthesised reference material for the support of LC-MS/MS-based drug testing. Anal. Bioanal. Chem. 2011, 401, 493.
28. M.A. ElSohly, W. Gul, K.M. Elsohly, T.P. Murphy, V.L. Madgula, S.I. Khan. Liquid chromatography-tandem mass spectrometry analysis of urine specimens for K2 (JWH-018) metabolites. J. Anal. Toxicol. 2011, 35, 487.
29. K.C. Chimalakonda, C.L. Moran, P.D. Kennedy, G.W. Endres, A. Uzieblo, P.J. Dobrowolski, et al. Solid-phase extraction and quantitative measurement of omega and omega-1 metabolites of JWH-018 and JWH-073 in human urine. Anal. Chem. 2011, 83, 6381.
30. A. Grigoryev, S. Savchuk, A. Melnik, N. Moskaleva, J. Dzhurko, M. Ershov, et al. Chromatography-mass spectrometry studies on the metabolism of synthetic cannabinoids JWH-018 and JWH-073, psychoactive components of smoking mixtures. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2011, 879, 1126.
31. M. Hutter, S. Broecker, S. Kneisel, V. Auwärter. Identification of the major urinary metabolites in man of seven synthetic cannabinoids of the aminoalkylindole type present as adulterants in 'herbal mixtures' using LC-MS/MS techniques. J. Mass Spectrom. 2012, 47, 54.
32. A. Grigoryev, A. Melnik, S. Savchuk, A. Simonov, V. Rozhanets. Gas and liquid chromatography-mass spectrometry studies on the metabolism of the synthetic phenylacetylindole cannabimimetic JWH-250, the psychoactive component of smoking mixtures. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2011, 879, 2519.
33. A. Grigoryev, P. Kavanagh, A. Melnik. The detection of the urinary metabolites of 3-[(adamantan-1-yl)carbonyl]-1-pentylindole (AB-001), a novel cannabimimetic, by gas chromatography-mass spectrometry. Drug Test. Anal. 2012, 4, 519.
34. P. Kavanagh, A. Grigoryev, A. Melnik, A. Simonov. The identification of the urinary metabolites of 3-(4-methoxybenzoyl)-1-pentylindole (RCS-4), a novel cannabimimetic, by gas chromatography-mass spectrometry. J. Anal. Toxicol. 2012, 36, 303.
35. A. Grigoryev, P. Kavanagh, A. Melnik. The detection of the urinary metabolites of 1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone (AM-694), a high affinity cannabimimetic, by gas chromatography - mass spectrometry. Drug Test. Anal. 2012, DOI: 10.1002/dta.1336.
36. U. Kim, M.J. Jin, J. Lee, S.B. Han, M.K. In, H.H. Yoo. Tentative identification of phase I metabolites of HU-210, a classical synthetic cannabinoid, by LC-MS/MS. J. Pharm. Biomed. Anal. 2012, 64/65, 26.
37. World Anti-Doping Agency. The 2012 Prohibited List. International Standard. Available at: http://www.wada-ama.org/Documents/World_Anti-Doping_Program/WADP-Prohibited-list/2012/WADA_Prohibited_List_2012_EN.pdf [12 June 2012].
38. Cayman Chemical Website. Available at: https://www.caymanchem.com/app/template/Search.vm# searchTerm=cannabinoid+metabolite [12 June 2012].
39. A. Makriyannis, H. Deng. Cannabimimetic indole derivatives. World Patent No. 2001028557 A1 20010426, 2001.
40. 2 cannabinoid receptor activity. J. Med. Chem. 2010, 53, 295.
41. Cayman Spectral Library. Available at: https://www.caymanchem.com/app/template/SpectralLibrary.vm [21 August 2012].
42. A. Wintermeyer, I. Möller, M. Thevis, M. Jübner, J. Beike, M.A. Rothschild, et al. In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Anal. Bioanal. Chem. 2010, 398, 2141.
43. 2) by HPLC-MS/MS. Anal. Bioanal. Chem. 2006, 386, 1345.
44. E.D. Kharasch, K.E. Thummel. Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane. Anesthesiology 1993, 79, 795.
45. K.E. Thummel, E.D. Kharasch, T. Podoll, K. Kunze. Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1. Drug Metab. Dispos. 1993, 21(2), 350.
46. M.T. Baker, J.N. Bates, S.V. Leff. Comparative defluorination and cytochrome P-450 loss by the microsomal metabolism of fluoro- and fluorochloroethenes. Drug Metab. Dispos. 1987, 15, 499.