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Anal Bioanal Chem (2013) 405:31253135 DOI 10.1007/s00216-013-6741-4
RESEARCH PAPER
2-Methiopropamine, a thiophene analogue of methamphetamine: studies on its metabolism and detectability in the ratand human using GC-MS and LC-(HR)-MS techniques
Jessica Welter & Markus R. Meyer & Ehud (Udi) Wolf &
Wolfgang Weinmann & Pierce Kavanagh &
Hans H. Maurer
Received: 27 November 2012 /Revised: 7 January 2013 /Accepted: 12 January 2013 /Published online: 30 January 2013 # Springer-Verlag Berlin Heidelberg 2013
Abstract 2-Methiopropamine [1-(thiophen-2-yl)-2-methylaminopropane, 2-MPA], a thiophene analogue of methamphetamine, is available from online vendors selling research chemicals. The first samples were seized by the German police in 2011. As it is a recreational stimulant, its inclusion in routine drug screening protocols should be required. The aims of this study were to identify the phase I and II metabolites of 2-MPA in rat and human urine and to identify the human cytochrome-P450 (CYP) isoenzymes involved in its phase I metabolism. In addition, the detectability of 2-MPA in urine samples using the authors well-established gas chromatographymass spectrometry (GCMS) and liquid chromatography-linear ion trap-mass spec-trometry (LC-MSn) screening protocols was also evaluated. The metabolites were isolated from rat and human urine
samples by solid-phase extraction without or following enzymatic cleavage of conjugates. The phase I metabolites, following acetylation, were separated and identified by GCMS and/or liquid chromatographyhigh-resolution linear ion trap mass spectrometry (LC-HR-MSn) and the phase II metabolites by LC-HR-MSn. The following major metabolic pathways were proposed: N-demethylation, hydroxylation at the side chain and at the thiophene ring, and combination of these transformations followed by glucuronidation and/or sulfation. CYP1A2, CYP2C19, CYP2D6, and CYP3A4 were identified as the major phase I metabolizing enzymes. They were also involved in the N-demethylation of the analogue methamphetamine and CYP2C19, CYP2D6, and CYP3A4 in its ring hydroxylation. Following the administration of a typical users dose, 2-MPA and its metabolites were identified in rat urine using the authors GC-MS and the LC-MSn screening approaches. Ingestion of 2-MPA could also be detected by both protocols in an authentic human urine sample.
Keywords Designer drugs . Methiopropamine . 2-MPA . Cytochrome-P450 . GC-MS . LC-MS
Introduction
2-Methiopropamine [1-(thiophen-2-yl)-2-methylaminopro-pane, 2-MPA] is a methamphetamine (MA) analogue in which the benzene ring is bioisosterically exchanged with a thiophene ring. It was first synthesized in 1942 by Blicke and...