title: 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.
abstract: This pilot study was performed to study the main metabolic reactions of four synthetic cannabinoids: JWH-015, JWH-098, JWH-251, and JWH-307 in order to setup a screening method for the detection of main metabolites in biological fluids. In silico prediction of main metabolic reactions was performed using MetaSite(™) software. To evaluate the agreement between software prediction and experimental reactions, we performed in vitro experiments on the same JWHs using rat liver slices. The obtained samples were analyzed by liquid chromatography-quadrupole time-of-flight and the identification of metabolites was executed using Mass-MetaSite(™) software that automatically assigned the metabolite structures to the peaks detected based on their accurate masses and fragmentation. A comparison between the experimental findings and the in silico metabolism prediction using MetaSite(™) software showed a good accordance between experimental and in silico data. Thus, the use of in silico metabolism prediction might represent a useful tool for the forensic and clinical toxicologist to identify possible main biomarkers for synthetic cannabinoids in biological fluids, especially urine, following their administration.
authors.affiliation: Institute of Public Health, Catholic University of Sacred Heart, 00198, Rome, Italy, sabina.stranorossi@gmail.com.
authors.forename: Sabina
authors.initials: S
authors.lastname: Strano-Rossi
authors.forename: Luca
authors.initials: L
authors.lastname: Anzillotti
authors.forename: Stefania
authors.initials: S
authors.lastname: Dragoni
authors.forename: Roberto Maria
authors.initials: RM
authors.lastname: Pellegrino
authors.forename: Laura
authors.initials: L
authors.lastname: Goracci
authors.forename: Vincenzo Lorenzo
authors.initials: VL
authors.lastname: Pascali
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D002186:Cannabinoids / Q000032:analysis*; D002853:Chromatography, Liquid; D053593:Forensic Toxicology / Q000379:methods; D006801:Humans; D007211:Indoles / Q000032:analysis*; D008099:Liver / Q000378:metabolism; D008956:Models, Chemical; D009281:Naphthalenes / Q000032:analysis*; D010865:Pilot Projects; D011758:Pyrroles / Q000032:analysis*; D051381:Rats; D012984:Software; D015813:Substance Abuse Detection / Q000379:methods*; D053719:Tandem Mass Spectrometry; D016482:Urinalysis
chemical_list: C586414:1-(1-pentyl-1H-indol-3-yl)-2-o-tolylethanone; D015415:Biomarkers; D002186:Cannabinoids; D007211:Indoles; D009281:Naphthalenes; D011758:Pyrroles; C402944:JHW 015