Lefetamine‐derived designer drugs <i>N</i>‐ethyl‐1,2‐diphenylethylamine (NEDPA) and <i>N‐iso</i>‐propyl‐1,2‐diphenylethylamine (NPDPA): Metabolism and detectability in rat urine using GC‐MS, LC‐MS<sup>n</sup> and LC‐HR‐MS/MS

Drug Testing and Analysis - Tập 6 Số 10 - Trang 1038-1048 - 2014
Carina S. D. Wink1, Golo M. J. Meyer1, Dirk K. Wissenbach1, Andrea Jacobsen‐Bauer2, Markus R. Meyer1, Hans H. Maurer1
1Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421 Homburg (Saar), Germany
2Landeskriminalamt Baden-Württemberg; D-70372 Stuttgart Germany

Tóm tắt

N‐Ethyl‐1,2‐diphenylethylamine (NEDPA) and N‐iso‐propyl‐1,2‐diphenylethylamine (NPDPA) are two designer drugs, which were confiscated in Germany in 2008. Lefetamine (N,N‐dimethyl‐1,2‐diphenylethylamine, also named L‐SPA), the pharmaceutical lead of these designer drugs, is a controlled substance in many countries. The aim of the present work was to study the phase I and phase II metabolism of these drugs in rats and to check for their detectability in urine using the authors’ standard urine screening approaches (SUSA). For the elucidation of the metabolism, rat urine samples were worked up with and without enzymatic cleavage, separated and analyzed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐high resolution‐tandem mass spectrometry (LC‐HR‐MS/MS). According to the identified metabolites, the following metabolic pathways for NEDPA and NPDPA could be proposed: N‐dealkylation, mono‐ and bis‐hydroxylation of the benzyl ring followed by methylation of one of the two hydroxy groups, combinations of these steps, hydroxylation of the phenyl ring after N‐dealkylation, glucuronidation and sulfation of all hydroxylated metabolites. Application of a 0.3 mg/kg BW dose of NEDPA or NPDPA, corresponding to a common lefetamine single dose, could be monitored in rat urine using the authors’ GC‐MS and LC‐MSn SUSA. However, only the metabolites could be detected, namely N‐deethyl‐NEDPA, N‐deethyl‐hydroxy‐NEDPA, hydroxy‐NEDPA, and hydroxy‐methoxy‐NEDPA or N‐de‐iso‐propyl‐NPDPA, N‐de‐iso‐propyl‐hydroxy‐NPDPA, and hydroxy‐NPDPA. Assuming similar kinetics, an intake of these drugs should also be detectable in human urine. Copyright © 2014 John Wiley & Sons, Ltd.

Từ khóa


Tài liệu tham khảo

10.1016/0031-6989(85)90082-7

10.1016/0376-8716(94)90096-5

10.1016/0376-8716(89)90071-9

Westphal F., 2010, Lefetamin‐Derivate: alte Bekannte neu auf dem Drogenmarkt, Toxichem Krimtech, 77, 46

Tainter M.L., 1943, Actions of a series of diphenyl‐ethylamines, J. Pharmacol. Exp. Ther., 77, 317

10.1016/j.bmc.2009.03.025

Bluelight.http://www.bluelight.org/vb/[14 February 2014].

Forum Opiophile.http://forum.opiophile.org/forum.php[14 February 2014].

Drug‐Forums.http://www.drugs‐forum.com/index.php[14 February 2014].

Maurer H.H., 2011, Mass Spectral and GC Data of Drugs, Poisons, Pesticides, Pollutants and their Metabolites

10.1007/s00216-011-5032-1

Bundesrepublik Deutschland.Tierschutzgesetz.http://www.gesetze‐im‐internet.de/bundesrecht/tierschg/gesamt.pdf 2013.

10.1007/s00216-013-6741-4

10.1002/jms.2960

10.1007/s00216-010-4398-9

National Institute of Standards and Technology.Automated Mass Spectral Deconvolution and Identification System (AMDIS).http://chemdata.nist.gov/mass‐spc/amdis/ 2012.

10.1373/clinchem.2009.135517

Maurer H.H., 2011, Mass Spectral Library of Drugs, Poisons, Pesticides, Pollutants and their Metabolites

Maurer H.H., 2014, Maurer/Wissenbach/Weber MWW LC‐MSn Library of Drugs, Poisons, and their Metabolites

McLafferty F.W., 1993, Interpretation of Mass Spectra

Smith R.M., 1999, Understanding Mass Spectra ‐ A Basic Approach

10.1016/S0378-4347(00)00025-6

10.1021/tx900134e

10.1016/S1387-3806(98)14066-6

10.1002/hlca.19730560728

10.1255/ejms.566

10.1111/j.1476-5381.2009.00267.x

10.1002/jms.2027

Thông tin
Thông tin xuất bản

Drug Testing and Analysis

Tập 6 Số 10

1038-1048

Thông tin tác giả