title: In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS.
abstract: One of the main challenges posed by the emergence of new psychoactive substances is their identification in human biological samples. Trying to detect the parent drug could lead to false-negative results when the delay between consumption and sampling has been too long. The identification of their metabolites could then improve their detection window in biological matrices. Oxidative metabolism by cytochromes P450 and glucuronidation are two major detoxification pathways in humans. In order to characterize possible CYP- and UGT-dependent metabolites of the 2-(4-bromo-2,5-dimethoxy-phenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25B-NBOMe), a synthetic psychoactive drug, analyses of human liver microsome (HLM) incubates were performed using an ultra-high performance liquid chromatography system coupled with a quadrupole-time of flight mass spectrometry detector (UHPLC-Q-TOF/MS). On-line analyses were performed using a Waters OASIS HLB column (30 x 2.1 mm, 20 µm) for the automatic sample loading and a Waters ACQUITY HSS C18 column (150 x 2 mm, 1.8 µm) for the chromatographic separation. Twenty-one metabolites, consisting of 12 CYP-derived and 9 UGT-derived metabolites, were identified. O-Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe-intoxication case reports. Although other important metabolic transformations, such as sulfation, acetylation, methylation or glutathione conjugation, were not studied and artefactual metabolites might have been produced during the HLM incubation process, the record of all the metabolite MS spectra in our library should enable us to characterize relevant metabolites of 25B-NBOMe and allow us to detect 25B-MBOMe users.
authors.affiliation: Laboratoire de thermodynamique et modélisation moléculaire, Faculté de chimie, USTHB, BP 32 El-Alia, 16111 Bab-Ezzouar, Alger, Algérie.|Institut National de Criminalistique et de Criminologie (INCC/GN), Bouchaoui, Alger, Algérie.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Boumrah
authors.affiliation: Laboratoire de Toxicologie, Pôle de Biologie-Pathologie-Génétique du CHRU de Lille, Bd du Prof. J. Leclercq, 59037, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Humbert
authors.affiliation: Laboratoire de Toxicologie, Pôle de Biologie-Pathologie-Génétique du CHRU de Lille, Bd du Prof. J. Leclercq, 59037, Lille, France.
authors.forename: Melodie
authors.initials: M
authors.lastname: Phanithavong
authors.affiliation: Ecole Militaire Polytechnique EMP, BP 17 Bordj-El-Bahri, Alger, Algérie.
authors.forename: Kamel
authors.initials: K
authors.lastname: Khimeche
authors.affiliation: Laboratoire de thermodynamique et modélisation moléculaire, Faculté de chimie, USTHB, BP 32 El-Alia, 16111 Bab-Ezzouar, Alger, Algérie.
authors.forename: Abdallah
authors.initials: A
authors.lastname: Dahmani
authors.affiliation: Laboratoire de Toxicologie, Pôle de Biologie-Pathologie-Génétique du CHRU de Lille, Bd du Prof. J. Leclercq, 59037, Lille, France.|EA4483, Université de Lille 2, 59045, Lille, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Allorge
mesh_terms: D000107:Acetylation; D000840:Anisoles / Q000032:analysis / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015198:Designer Drugs / Q000032:analysis / Q000493:pharmacokinetics*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008745:Methylation; D008862:Microsomes, Liver / Q000378:metabolism; D010627:Phenethylamines / Q000032:analysis / Q000493:pharmacokinetics*; D011619:Psychotropic Drugs / Q000032:analysis / Q000493:pharmacokinetics*; D015813:Substance Abuse Detection / Q000379:methods; D013431:Sulfates / Q000378:metabolism; D053719:Tandem Mass Spectrometry
chemical_list: D000840:Anisoles; D015198:Designer Drugs; D010627:Phenethylamines; D011619:Psychotropic Drugs; D013431:Sulfates; D003577:Cytochrome P-450 Enzyme System; D014453:Glucuronosyltransferase; D005978:Glutathione; C000595926:2-(4-bromo-2,5-dimethoxyphenyl)-N-((2-methoxyphenyl)methyl)ethanamine
keywords: 25B-NBOMe; UHPLC-Q-TOF/MS; human liver microsomes; in vitro; metabolism