title: New cathinone-derived designer drugs 3-bromomethcathinone and 3-fluoromethcathinone: studies on their metabolism in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS and their detectability in urine.
abstract: 3-Bromomethcathinone (3-BMC) and 3-Fluoromethcathinone (3-FMC) are two new designer drugs, which were seized in Israel during 2009 and had also appeared on the illicit drug market in Germany. These two compounds were sold via the Internet as so-called "bath salts" or "plant feeders." The aim of the present study was to identify for the first time the 3-BMC and 3-FMC Phase I and II metabolites in rat urine and human liver microsomes using GC-MS and LC-high-resolution MS (HR-MS) and to test for their detectability by established urine screening approaches using GC-MS or LC-MS. Furthermore, the human cytochrome-P450 (CYP) isoenzymes responsible for the main metabolic steps were studied to highlight possible risks of consumption due to drug-drug interaction or genetic variations. For the first aim, rat urine samples were extracted after and without enzymatic cleavage of conjugates. The metabolites were separated and identified by GC-MS and by LC-HR-MS. The main metabolic steps were N-demethylation, reduction of the keto group to the corresponding alcohol, hydroxylation of the aromatic system and combinations of these steps. The elemental composition of the metabolites identified by GC-MS could be confirmed by LC-HR-MS. Furthermore, corresponding Phase II metabolites were identified using the LC-HR-MS approach. For both compounds, detection in rat urine was possible within the authors' systematic toxicological analysis using both GC-MS and LC-MS(n) after a suspected recreational users dose. Following CYP enzyme kinetic studies, CYP2B6 was the most relevant enzyme for both the N-demethylation of 3-BMC and 3-FMC after in vitro-in vivo extrapolation.
authors.affiliation: Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421 Homburg (Saar), Germany. markus.meyer@uks.eu
authors.forename: Markus R
authors.initials: MR
authors.lastname: Meyer
authors.forename: Christian
authors.initials: C
authors.lastname: Vollmar
authors.forename: Andrea E
authors.initials: AE
authors.lastname: Schwaninger
authors.forename: Ehud
authors.initials: E
authors.lastname: Wolf
authors.forename: Hans H
authors.initials: HH
authors.lastname: Maurer
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D002853:Chromatography, Liquid / Q000379:methods*; D065702:Cytochrome P-450 CYP2B6; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D015198:Designer Drugs / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D011427:Propiophenones / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D051381:Rats
chemical_list: C571631:3-bromomethcathinone; D000470:Alkaloids; D015198:Designer Drugs; D011427:Propiophenones; C023665:cathinone; C571632:3-fluoromethcathinone; D001189:Aryl Hydrocarbon Hydroxylases; C585599:CYP2B6 protein, human; D065702:Cytochrome P-450 CYP2B6; D019389:Cytochrome P-450 CYP2D6; D010089:Oxidoreductases, N-Demethylating