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

Drug Testing and Analysis - Tập 4 Số 10 - Trang 745-753 - 2012
Tim Sobolevsky1, Ilya Prasolov1, Г. М. Родченков1
1Moscow Antidoping Centre 105005 Moscow Elizavetinsky per. 10 Russia

Tóm tắt

Synthetic cannabinoids are the psychotropic compounds frequently identified as active components of smoking mixtures easily available via the Internet in several countries. These herbal blends have become extremely popular as a legal alternative to cannabis‐based products and are difficult to detect by regular drug tests.Here we report on an in vitro and in vivo metabolism of AM‐2201, 1‐[(5‐fluoropentyl)‐1H‐indol‐3‐yl]‐(naphthalen‐1‐yl)methanone, and UR‐144 (KM‐X1), (1‐pentylindol‐3‐yl)‐(2,2,3,3‐tetramethylcyclopropyl)methanone isolated using preparative liquid chromatography from the smoking mixtures sold in Russia. After incubation with human liver microsomes (HLM) as well as with cytochrome isoenzymes 3A4 and 2B6, the metabolic pathways were identified by means of liquid chromatography – triple quadrupole and high resolution mass spectrometry with electrospray ionization in positive mode. It was found that the in vitro reactions include mono‐ and dihydroxylation, loss of N‐alkyl side chain and formation of dihydrodiol metabolites in case of AM‐2201. The HLM were found to be superior over the other two isoenzymes for generation of cannabinoid metabolites. Finally, forensic urine samples were analyzed to validate the in vitro data and it has been shown that for both cannabimimetics the recommended screening targets are the monohydroxylated metabolites. Copyright © 2012 John Wiley & Sons, Ltd.

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Tài liệu tham khảo

10.1002/jms.1811

10.1093/jat/34.5.252

10.1007/s11419-011-0108-3

10.1016/j.forsciint.2011.07.011

10.1007/s11419-012-0137-6

10.1016/j.forsciint.2011.12.010

10.1007/s11419-011-0114-5

10.1007/s11419-011-0130-5

10.1248/cpb.59.1203

10.1007/s11419-012-0136-7

10.1016/j.forsciint.2010.01.004

10.1002/dta.268

10.1093/jat/bks047

10.1016/j.forsciint.2011.03.031

10.1016/j.forsciint.2011.03.020

10.1093/anatox/35.6.360

10.1007/s11419-010-0100-3

10.1002/jms.2059

10.1002/jms.1877

10.1002/dta.342

10.1016/j.jchromb.2010.03.016

10.1093/jat/bks048

10.1093/anatox/35.7.386

10.1093/anatox/35.7.424

10.1016/j.forsciint.2010.04.003

10.1002/dta.158

10.1007/s00216-011-4931-5

10.1093/anatox/35.7.487

10.1021/ac201377m

10.1016/j.jchromb.2011.03.034

10.1002/jms.2026

10.1016/j.jchromb.2011.07.004

10.1002/dta.350

10.1093/jat/bks032

10.1002/dta.1336

10.1016/j.jpba.2012.02.007

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].

Cayman Chemical Website. Available at:https://www.caymanchem.com/app/template/Search.vm# searchTerm = cannabinoid + metabolite[12 June 2012].

A.Makriyannis H.Deng.Cannabimimetic indole derivatives. World Patent No. 2001028557 A1 20010426 2001.

10.1021/jm901214q

Cayman Spectral Library. Available at:https://www.caymanchem.com/app/template/SpectralLibrary.vm[21 August 2012].

10.1007/s00216-010-4171-0

10.1007/s00216-006-0717-6

10.1097/00000542-199310000-00023

Thummel K.E., 1993, Human liver microsomal enflurane defluorination catalyzed by cytochrome P‐450 2E1, Drug Metab. Dispos., 21, 350

Baker M.T., 1987, Comparative defluorination and cytochrome P‐450 loss by the microsomal metabolism of fluoro‐ and fluorochloroethenes, Drug Metab. Dispos., 15, 499

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Drug Testing and Analysis

Tập 4 Số 10

745-753

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