title: N-methyl-N-trimethylsilyltrifluoroacetamide-promoted synthesis and mass spectrometric characterization of deuterated ephedrines.
abstract: Synthesis and mass spectrometric characterization of drugs or metabolites labeled by stable isotopes has been of great interest in fields of clinical, forensic and doping control analysis. Deuterated ephedrine and p-hydroxypseudoephedrine were prepared from corresponding amines by a novel procedure utilizing N- methyl-N-trimethylsilyltrifluoroacetamide and deuterated iodomethane. The mechanism of methylation was studied by mass spectrometry using phenylethylamine as a model compound, and a rearrangement based on an intermediate six-membered ring structure with a trimethylsilyl-enol-ether is proposed giving rise to a leaving group of trimethyliodosilane and the desired monomethylated product. Deuterated analogues to frequently quantitated ephedrines were readily synthesized with purities >90%, and mass spectra recorded under different ionization and dissociation conditions presented distinct fragmentation processes including eliminations of water and methylamine as well as the generation of a benzyl cation.
authors.affiliation: Institute of Biochemistry, German Sport University Cologne, Carl-Diem Weg 6, 50933 Cologne, Germany. m.thevis@biochem.dshs- koeln.de
authors.forename: Mario
authors.initials: M
authors.lastname: Thevis
authors.forename: Georg
authors.initials: G
authors.lastname: Opfermann
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Schänzer
mesh_terms: D000081:Acetamides; D000697:Central Nervous System Stimulants / Q000138:chemical synthesis / Q000737:chemistry; D003903:Deuterium / Q000737:chemistry; D004809:Ephedrine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D005463:Fluoroacetates; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D007553:Isotope Labeling; D008745:Methylation; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D014269:Trifluoroacetic Acid / Q000737:chemistry*; D014297:Trimethylsilyl Compounds / Q000737:chemistry*
chemical_list: D000081:Acetamides; D000697:Central Nervous System Stimulants; D005463:Fluoroacetates; D014297:Trimethylsilyl Compounds; C086665:N-methyl-N-(trimethylsilyl)trifluoroacetamide; D003903:Deuterium; D014269:Trifluoroacetic Acid; D004809:Ephedrine