• Home
  • Search Results
  • 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

Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Chloroform-d, 99.8 atom % D
Sigma-Aldrich
Acetonitrile, anhydrous, 99.8%
Sigma-Aldrich
Acetonitrile, HPLC Plus, ≥99.9%
Sigma-Aldrich
Chloroform, contains 100-200 ppm amylenes as stabilizer, ≥99.5%
Sigma-Aldrich
Formic acid, reagent grade, ≥95%
Sigma-Aldrich
N,N-Diisopropylethylamine, ReagentPlus®, ≥99%
Sigma-Aldrich
Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Chloroform-d, 99.8 atom % D, contains 0.03 % (v/v) TMS
Sigma-Aldrich
Acetonitrile, ACS reagent, ≥99.5%
Sigma-Aldrich
N,N-Diisopropylethylamine, purified by redistillation, 99.5%
Sigma-Aldrich
Chloroform, anhydrous, contains amylenes as stabilizer, ≥99%
Sigma-Aldrich
Formic acid, puriss. p.a., ACS reagent, reag. Ph. Eur., ≥98%
Sigma-Aldrich
Chloroform, suitable for HPLC, ≥99.8%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Chloroform, HPLC Plus, for HPLC, GC, and residue analysis, ≥99.9%, contains amylenes as stabilizer
Sigma-Aldrich
Acetonitrile, for HPLC, for UV, ≥99.9% (GC)
Sigma-Aldrich
Formic acid, ACS reagent, ≥96%
Sigma-Aldrich
Acetonitrile, suitable for HPLC, gradient grade, ≥99.9%
Sigma-Aldrich
Oxalic acid, 98%
Sigma-Aldrich
Oxalic acid, puriss. p.a., anhydrous, ≥99.0% (RT)
Sigma-Aldrich
Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC
Sigma-Aldrich
Oxalic acid dihydrate, ACS reagent, ≥99%
Sigma-Aldrich
Formic acid, puriss., meets analytical specifications of DAC, FCC, 98.0-100%
Sigma-Aldrich
Chloroform, contains ethanol as stabilizer, ACS reagent, ≥99.8%
Sigma-Aldrich
Chloroform-d, "100%", 99.96 atom % D
Supelco
1,2,4,5-Tetrachloro-3-nitrobenzene, Standard for quantitative NMR, TraceCERT®
Sigma-Aldrich
Chloroform-d, 99.8 atom % D, contains 1 % (v/v) TMS
Sigma-Aldrich
Chloroform-d, ≥99.8 atom % D, contains 0.5 wt. % silver foil as stabilizer
Sigma-Aldrich
Chloroform, suitable for HPLC, ≥99.8%, amylene stabilized
Sigma-Aldrich
Oxalic acid, ReagentPlus®, ≥99%