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 chromatography–mass spectrometry (GC-MS) and liquid chromatography-linear ion trap-mass spectrometry (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 GC-MS and/or liquid chromatography–high-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 user’s 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.
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References
Blicke FF, Burkhalter JH (1942) J Am Chem Soc 64:477–480
Schaeper J, Westphal F, Girreser U (2011) Toxichem Krimtech 78:480–488
Casale JF, Hays PA (2011) Microgram J 8:53–57
Maurer HH, Pfleger K, Weber AA (2011) Mass spectral library of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim
Wissenbach DK, Meyer MR, Remane D, Weber AA, Maurer HH (2011) Anal Bioanal Chem 400:79–88
Wissenbach DK, Meyer MR, Remane D, Philipp AA, Weber AA, Maurer HH (2011) Anal Bioanal Chem 400:3481–3489
Angelov D, O'Brien J, Kavanagh P (2013) Drug Test Anal. doi:10.1002/dta.298
Meyer MR, Vollmar C, Schwaninger AE, Maurer HH (2012) J Mass Spectrom 47:253–262
Meyer MR, Dinger J, Schwaninger AE, Wissenbach DK, Zapp J, Fritschi G, Maurer HH (2012) Anal Bioanal Chem 402:1249–1255
Maurer HH, Pfleger K, Weber AA (2011) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim
Ewald AH, Ehlers D, Maurer HH (2008) Anal Bioanal Chem 390:1837–1842
Meyer MR, Peters FT, Maurer HH (2010) Clin Chem 56:575–584
McLafferty FW, Turecek F (1993) Interpretation of mass spectra. University Science Books, Mill Valley
Smith RM, Busch KL (1999) Understanding mass spectra—a basic approach. Wiley, New York
de-Zeeuw RA, Franke JP, Maurer HH, Pfleger K (1992) Gas chromatographic retention indices of toxicologically relevant substances and their metabolites (report of the DFG Commission for Clinical Toxicological Analysis, special issue of the TIAFT bulletin). VCH, Weinheim
Mansuy D, Dansette PM, Foures C, Jaouen M, Moinet G, Bayer N (1984) Biochem Pharmacol 33:1429–1435
Mori Y, Kuroda N, Sakai Y, Yokoya F, Toyoshi K, Baba S (1985) Drug Metab Dispos 13:239–245
Fouda HG, Avery MJ, Dalvie D, Falkner FC, Melvin LS, Ronfeld RA (1997) Drug Metab Dispos 25:140–148
Sharma V, McNeill JH (2009) Br J Pharmacol 157:907–921
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The authors like to thank Gabriele Ulrich, Carsten Schröder, and Armin A. Weber for their support.
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Welter, J., Meyer, M.R., Wolf, E. et al. 2-Methiopropamine, a thiophene analogue of methamphetamine: studies on its metabolism and detectability in the rat and human using GC-MS and LC-(HR)-MS techniques. Anal Bioanal Chem 405, 3125–3135 (2013). https://doi.org/10.1007/s00216-013-6741-4
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DOI: https://doi.org/10.1007/s00216-013-6741-4