Metabolic fate, mass spectral fragmentation, detectability, and differentiation in urine of the benzofuran designer drugs 6-APB and 6-MAPB in comparison to their 5-isomers using GC-MS and LC-(HR)-MSn techniques
- 649 Downloads
The number of so-called new psychoactive substances (NPS) is still increasing by modification of the chemical structure of known (scheduled) drugs. As analogues of amphetamines, 2-aminopropyl-benzofurans were sold. They were consumed because of their euphoric and empathogenic effects. After the 5-(2-aminopropyl)benzofurans, the 6-(2-aminopropyl)benzofuran isomers appeared. Thus, the question arose whether the metabolic fate, the mass spectral fragmentation, and the detectability in urine are comparable or different and how an intake can be differentiated. In the present study, 6-(2-aminopropyl)benzofuran (6-APB) and its N-methyl derivative 6-MAPB (N-methyl-6-(2-aminopropyl)benzofuran) were investigated to answer these questions. The metabolites of both drugs were identified in rat urine and human liver preparations using GC-MS and/or liquid chromatography-high resolution-mass spectrometry (LC-HR-MSn). Besides the parent drug, the main metabolite of 6-APB was 4-carboxymethyl-3-hydroxy amphetamine and the main metabolites of 6-MAPB were 6-APB (N-demethyl metabolite) and 4-carboxymethyl-3-hydroxy methamphetamine. The cytochrome P450 (CYP) isoenzymes involved in the 6-MAPB N-demethylation were CYP1A2, CYP2D6, and CYP3A4. An intake of a common users’ dose of 6-APB or 6-MAPB could be confirmed in rat urine using the authors’ GC-MS and the LC-MSn standard urine screening approaches with the corresponding parent drugs as major target allowing their differentiation. Furthermore, a differentiation of 6-APB and 6-MAPB in urine from their positional isomers 5-APB and 5-MAPB was successfully performed after solid phase extraction and heptafluorobutyrylation by GC-MS via their retention times.
KeywordsDesigner drugs 6-APB 6-MAPB Metabolism GC-MS LC-(HR)-MSn
The authors like to thank Achim Caspar, Julia Dinger, Andreas Helfer, Julian Michely, Carina Wink, Gabriele Ulrich, Carsten Schröder, and Armin A. Weber for the support and/or helpful discussion.
- 1.European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) (2014) European Drug Report: Trends and developments. http://www.emcdda.europa.eu/attachements.cfm/att_228272_EN_TDAT14001ENN.pdf
- 2.Welter J, Kavanagh P, Meyer MR, Maurer HH (2015) Benzofuran analogues of amphetamine and methamphetamine: studies on the metabolism and toxicological analysis of 5-APB and 5-MAPB in urine and plasma using GC-MS and LC-(HR)-MSn techniques. Anal Bioanal Chem. doi: 10.1007/s00216-014-8360-0 Google Scholar
- 3.Advisory Council on the Misuse of Drugs (ACMD) (2013) Benzofurans: A review of the evidence of use and harm. https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/261783/Benzofuran_compounds_report.pdf
- 7.Casale JF, Hays PA (2012) The characterization of 6-(2-aminopropyl)benzofuran and differentiation from its 4-, 5-, and 7-positional analogues. Microgram J 9:61–74Google Scholar
- 9.Maurer HH, Pfleger K, Weber AA (2011) Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites. Wiley-VCH, Weinheim (Germany)Google Scholar
- 16.Meyer MR, Vollmar C, Schwaninger AE, Maurer HH (2012) 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. J Mass Spectrom 47:253–262CrossRefGoogle Scholar
- 17.Connelly JC, Connor SC, Monte S, Bailey NJ, Borgeaud N, Holmes E, Troke J, Nicholson JK, Gavaghan CL (2002) Application of directly coupled high performance liquid chromatography-NMR-mass spectometry and 1H NMR spectroscopic studies to the investigation of 2,3-benzofuran metabolism in Sprague-Dawley rats. Drug Metab Dispos 30:1357–1363CrossRefGoogle Scholar
- 18.Kobayashi T, Sugihara J, Harigaya S (1987) Mechanism of metabolic cleavage of a furan ring. Drug Metab Dispos 15:877–881Google Scholar
- 23.McLafferty FW, Turecek F (1993) Interpretation of Mass Spectra. University Science Books, Mill ValleyGoogle Scholar
- 24.Smith RM, Busch KL (1999) Understanding mass spectra—a basic approach. Wiley, New YorkGoogle Scholar
- 25.Helfer AG, Turcant A, Boels D, Ferec S, Lelievre B, Welter J, Meyer MR, Maurer HH (2014) Elucidation of the metabolites of the novel psychoactive substance 4-methyl-N-ethyl-cathinone (4-MEC) in human urine and pooled liver microsomes by GC-MS and LC-HR-MS/MS techniques and of its detectability by GC-MS or LC-MSn standard screening approaches. Drug Test Anal. doi: 10.1002/dta.1682 Google Scholar