Skip to Content
Merck
  • Lefetamine, a controlled drug and pharmaceutical lead of new designer drugs: synthesis, metabolism, and detectability in urine and human liver preparations using GC-MS, LC-MS(n), and LC-high resolution-MS/MS.

Lefetamine, a controlled drug and pharmaceutical lead of new designer drugs: synthesis, metabolism, and detectability in urine and human liver preparations using GC-MS, LC-MS(n), and LC-high resolution-MS/MS.

Analytical and bioanalytical chemistry (2015-01-13)
Carina S D Wink, Golo M J Meyer, Josef Zapp, Hans H Maurer
ABSTRACT

Lefetamine (N,N-dimethyl-1,2-diphenylethylamine, L-SPA) was marketed as an opioid analgesic in Japan and Italy. After being widely abused, it became a controlled substance. It seems to be a pharmaceutical lead for designer drugs because N-ethyl-1,2-diphenylethylamine (NEDPA) and N-iso-propyl-1,2-diphenylethylamine (NPDPA) were confiscated by the German police. In contrast to these derivatives, metabolism and detectability of lefetamine were not studied yet. Therefore, phase I and II metabolism should be elucidated and correlated to the derivatives. Also the detectability using the authors' standard urine screening approaches (SUSA) needed to be checked. As lefetamine was commercially unavailable, it had to be synthesized first. For metabolism studies, a high dose of lefetamine was administered to rats and the urine samples worked up in different ways. Separation and analysis were achieved by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS). In accordance with NEPDA and NPDPA, the following metabolic steps could be proposed: N-oxidation, N-dealkylation, mono- and bis-hydroxylation of the benzene ring, and hydroxylation of the phenyl ring only after N-dealkylation. The di-hydroxy metabolites were conjugated by methylation of one hydroxy group, and hydroxy metabolites by glucuronidation or sulfation. All initial metabolites could also be detected in human liver preparations. After a therapeutic lefetamine dose, the bis-nor, bis-nor-hydroxy, nor-hydroxy, nor-di-hydroxy metabolites could be detected using the authors' GC-MS SUSA and the nor-hydroxy-glucuronide by the LC-MS(n) SUSA. Thus, an intake of lefetamine should be detectable in human urine assuming similar pharmacokinetics.

MATERIALS
Product Number
Brand
Product Description

Supelco
1,2,4,5-Tetrachloro-3-nitrobenzene, Standard for quantitative NMR, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland
Sigma-Aldrich
Acetonitrile, electronic grade, 99.999% trace metals basis
Sigma-Aldrich
N,N-Diisopropylethylamine, purified by redistillation, 99.5%
Sigma-Aldrich
Formic acid solution, BioUltra, 1.0 M in H2O
Sigma-Aldrich
Formic acid, ≥95%, FCC, FG
Sigma-Aldrich
N,N-Diisopropylethylamine, ReagentPlus®, ≥99%
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Supelco
Residual Solvent - Chloroform, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Acetonitrile, analytical standard
Sigma-Aldrich
Ultrapure Acetonitrile
Sigma-Aldrich
Formic acid, ACS reagent, ≥96%
Sigma-Aldrich
Acetonitrile, ReagentPlus®, 99%
Sigma-Aldrich
Formic acid, reagent grade, ≥95%
Sigma-Aldrich
Acetonitrile, biotech. grade, ≥99.93%
Sigma-Aldrich
N,N-Diisopropylethylamine, 99.5%, biotech. grade
Sigma-Aldrich
Formic acid, ACS reagent, ≥88%
Supelco
Acetonitrile, Pharmaceutical Secondary Standard; Certified Reference Material
USP
Residual Solvent Class 2 - Acetonitrile, United States Pharmacopeia (USP) Reference Standard
Sigma-Aldrich
Acetonitrile, suitable for DNA synthesis, ≥99.9% (GC)
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%
Supelco
Oxalic acid concentrate, 0.1 M (COOH)2 (0.2N), eluent concentrate for IC
Sigma-Aldrich
Oxalic acid, purified grade, 99.999% trace metals basis
Sigma-Aldrich
Chloroform-d, 99.8 atom % D
Sigma-Aldrich
Chloroform-d, ≥99.8 atom % D, anhydrous
Sigma-Aldrich
Chloroform-d, 99.8 atom % D, contains 0.1 % (v/v) TMS
Sigma-Aldrich
Chloroform-d, 99.8 atom % D, contains 0.05 % (v/v) TMS
Sigma-Aldrich
Chloroform-d, "100%", 99.95 atom % D