Metabolism of JWH-015, JWH-098, JWH-251, and JWH-307 in silico and in vitro: A pilot study for the detection of unknown synthetic cannabinoids metabolites Forensic Toxicology

Analytical and Bioanalytical Chemistry

Volumn 406, Issue 15, 2014, Pages 3621-3636

  Strano Rossi, Sabina ^a   Anzillotti, Luca ^a   Dragoni, Stefania ^b   Pellegrino, Roberto Maria ^b   Goracci, Laura ^b   Pascali, Vincenzo Lorenzo ^a   Cruciani, Gabriele ^b  

^a CATHOLIC UNIVERSITY   (Italy)

^b UNIVERSITY OF PERUGIA   (Italy)

Author keywords

Forensic toxicology; In silico metabolism prediction; In vitro metabolism; Synthetic cannabinoids

Indexed keywords

BIOMOLECULES; BODY FLUIDS; FORECASTING; LIQUID CHROMATOGRAPHY; METABOLITES; PHYSIOLOGY;

BIOLOGICAL FLUIDS; FORENSIC TOXICOLOGY; IN-SILICO; IN-VITRO; METABOLIC REACTIONS; SCREENING METHODS; SYNTHETIC CANNABINOIDS; TIME OF FLIGHT;

METABOLISM;

1-(1-PENTYL-1H-INDOL-3-YL)-2-O-TOLYLETHANONE; BIOLOGICAL MARKER; CANNABINOID; INDOLE DERIVATIVE; JHW 015; NAPHTHALENE DERIVATIVE; PYRROLE DERIVATIVE;

ANIMAL; CHEMICAL MODEL; COMPUTER PROGRAM; FORENSIC TOXICOLOGY; HUMAN; LIQUID CHROMATOGRAPHY; LIVER; METABOLISM; PILOT STUDY; PROCEDURES; RAT; SUBSTANCE ABUSE; TANDEM MASS SPECTROMETRY; URINALYSIS;

ANIMALS; BIOLOGICAL MARKERS; CANNABINOIDS; CHROMATOGRAPHY, LIQUID; FORENSIC TOXICOLOGY; HUMANS; INDOLES; LIVER; MODELS, CHEMICAL; NAPHTHALENES; PILOT PROJECTS; PYRROLES; RATS; SOFTWARE; SUBSTANCE ABUSE DETECTION; TANDEM MASS SPECTROMETRY; URINALYSIS;

EID: 84901421270     PISSN: 16182642     EISSN: 16182650     Source Type: Journal    
DOI: 10.1007/s00216-014-7793-9     Document Type: Article

References (24)

1. UNODC (2013) The challenge of new psychoactive substances. http://www.unodc.org/documents/scientific/NPS-2013-SMART.pdf. Accessed 1 Feb 2014
2. Sobolevsky T, Prasolov I, Rodchenkov G (2010) Detection of JWH-018 metabolites in smoking mixture post-administration urine. Forensic Sci Int 200:141-147
3. Moran CL, Le VH, Chimalakonda KC, Smedley AL, Lackey FD, Owen SN, Kennedy PD, Endres GW, Ciske FL, Kramer JB, Kornilov AM, Bratton LD, Dobrowolski PJ, Wessinger WD, Fantegrossi WE, Prather PP, James LP, Radominska-Pandya A, Moran JH (2011) Quantitative measurement of JWH-018 and JWH-073 metabolites excreted in human urine. Anal Chem. doi: 10.1021/ac2005636
4. Möller I, Wintermeyer A, Bender K, Jübner M, Thomas A, Krug O, Schanzer W, Thevis M (2010) Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test Anal. doi: 10.1002/dta.158
5. Grigoryev A, Melnika A, Savchukb S, Simonovc A, Rozhanetsd V (2011) Gas and liquid chromatography-mass spectrometry studies on the metabolism of the synthetic phenylacetylindolecannabimimetic JWH-250, the psychoactive component of smoking mixtures. J Chromatogr B 879:2519-2526
6. Adamowicz P, Zuba D, Sekuła K (2013) Analysis of UR-144 and its pyrolysis product in blood and their metabolites in urine. Forensic Sci Int. doi: 10.1016/j.forsciint.2013.10.005
7. Kavanagh P, Grigoryev A, Melnik A, Savchuk S, Simonov A, Rozhanets V (2013) Detection and tentative identification of urinary phase I metabolites of phenylacetylindolecannabimimetics JWH-203 and JWH-251, by GC-MS and LC-MS/MS. J Chromatogr B Anal Technol Biomed Life Sci. doi: 10.1016/j.jchromb.2013.07.005
8. Kavanagh P, Grigoryev A, Melnik A, Simonov A (2012) 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. doi: 10.1093/jat/bks032
9. Grigoryev A, Kavanagh P, Melnik A, Savchuk S, Simonov A (2013) Gas and liquid chromatography-mass spectrometry detection of the urinary metabolites of UR-144 and its major pyrolysis product. J Anal Toxicol. doi: 10.1093/jat/bkt028
10. Grigoryev A, Kavanagh P, Melnik A (2013) 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. doi: 10.1002/dta.1336
11. Hutter M, Broecker S, Kneisel S, Auwärter V (2012) 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. doi: 10.1002/jms.2026
12. Grigoryev A, Kavanagh P, Melnik A (2012) 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. doi: 10.1002/dta.350
13. De Brabanter N, Esposito S, Tudela E, Lootens L, Meuleman P, Leroux-Roels G, Van Deventer K, Eenoo P (2013) In vivo and in vitro metabolism of the synthetic cannabinoid JWH-200. Rapid Commun Mass Spectrom. doi: 10.1002/rcm.6673
14. De Brabanter N, Esposito S, Geldof L, Lootens L, Meuleman P, Leroux-Roels G, Van Deventer K, Eenoo P (2013) In vivo and in vitro metabolism of JWH-122. Forensic Toxicol. doi: 10.1007/s11419-013-0179-4
15. Wintermeyer A, Möller I, Thevis M, Jübner M, Beike J, Rothschild MA, Bender K (2010) In vitro phase I metabolism of the synthetic cannabimimetic JWH-018. Anal Bioanal Chem. doi: 10.1007/s00216-010-4171-0
16. Zhang Q, Ma P, Cole RB, Wang G (2006) Identification of in vitro metabolites of JWH-015, an aminoalkylindole agonist for the peripheral cannabinoid receptor (CB2) by HPLC-MS/MS. Anal Bioanal Chem. doi: 10.1007/s00216-006-0717-6
17. Cruciani G, Carosati E, De Boeck B, Ethirajulu K, Mackie C, Howe T, Vianello R (2005) MetaSite: understanding metabolism in human cytochromes from the perspective of the chemist. J Med Chem 48:6970-6979
18. Cruciani G, Baroni M, Benedetti P, Goracci L, Fortuna CG (2013) Exposition and reactivity optimization to predict sites of metabolism in chemicals. Drug Discov Today Technol. doi: 10.1016/j.ddtec.2012.11.001
19. Zelesky V, Schneider R, Janiszewski J, Zamora I, Ferguson J, Troutman M (2013) Software automation tools for increased throughput metabolic soft-spot identification in early drug discovery. Bioanalysis. doi: 10.4155/bio.13.89
20. Tyrkko E, Pelander A, Ketola RA, Ojanpera I (2013) In silico and in vitro metabolism studies support identification of designer drugs in human urine by liquid chromatography/quadrupole-time of flight mass spectrometry. Anal Bioanal Chem 405:6697-6709
21. Bonn B, Leandersson C, Fontaine F, Zamora I (2010) Enhanced metabolite identification with MS(E) and a semi-automated software for structural elucidation. Rapid Commun Mass Spectrom. doi: 10.1002/rcm.4753
22. http://www.moldiscovery.com/soft-mass-MetaSite.php. Accessed 1 Feb 2014
23. de Graaf IA, Olinga P, de Jager MH, Merema MT, de Kanter R, van de Kerkhof EG, Groothuis GM (2010) Preparation and incubation of precision-cut liver and intestinal slices for application in drug metabolism and toxicity studies. Nat Protoc. doi: 10.1038/nprot.2010.111
24. Brandon EF, Raap CD, Meijerman I, Beijnen JH, Schellens JH (2003) An update on in vitro test methods in human hepatic drug biotransformation research: pros and cons. Toxicol Appl Pharmacol 189:233-246