Mass spectra ofN-[(S)-α-methoxy-α-(trifluoromethyl)phenylacetyl] derivatives of chiral amines. Stereochemistry of amphetamine metabolism in the rat

The electron impact mass spectra of the N-[(S)-α-methoxy-α-trifluoromethylphenylacetyl] derivatives of amphetamine and several related compounds have been studied with the purpose of developing an assay for the enantiomers of the amines based on selected ion monitoring gas chromatography mass spectrometry. Stable isotope labeled analogs were used to elucidate the fragmentation pattern. The molecular ions are present in the spectra but are weak. The 1-phenyl-1-methoxy-2,2,2-trifluoroethyl cation is of significant intensity in all of the spectra. Other major fragmentations include a McLafferty rearrangement to give styrene radical ions, α-cleavage to nitrogen, and formation of benzyl cations derived from the amine or aminoester portion. An analytical procedure was developed for the simultaneous determination of the concentration of the enantiomers of amphetamine in rat urine. The method is based on selected ion monitoring gas chromatographic mass spectrometric analysis of the N-[(S)-α-methoxy-α-(trifluoromethyl)phenylacetyl] derivatives and uses amphetamine labeled with deuterium in the methyl group as internal standard. Using this procedure it was found that rats administered racemic amphetamine intraperitoneally excrete slightly more of the S enantiomer than of the R.