Formation of an Interfering Substance, 3,4-Dimethyl-5 - Phenyl 1,3 - Oxazolidine, During A Pseudoephedrine Urinalysis

摘要

During fatal aviation accident investigations, bio-samples from the victims are submitted to the FAA Civil Aeromedical Institute for drug analysis. In the process of one such analysis, an unknown substance was found in a urine sample. Its initial analyses by thin layer chromatography and by liquid-liquid extraction/gas chromatography (GC) disclosed the presence of pseudoephedrine. Subsequent analyses of the reaccessioned sample by solid phase separation/GC fourier transform infrared/GC mass spectrometry indicated that the retention times of the unknown substance matched with those of pseudoephedrine. However, its infrared and mass spectra were different-the -OH and -NH- groups were missing, a C-O-C group was present, and the molar mass was 12 atomic mass units (amu) more than that of pseudoephedrine. A subsequent literature search suggested that ephedrine-like amines react with aldehydes to form oxazolidines. Therefore, the 12-amu increase could be accounted for by condensation of pseudoephedrine with formaldehyde. Since this aldehyde is present in various grades of methanol, and methanol was used during the solid phase separation, 3, 4-dimethyl-5- phenyl-1,3-oxazolidine was synthesized by using (+)- pseudoephedrine-HCl and formaldehyde. The analytical and spectral findings of the synthesized compound were consistent with those of the unknown interfering substance, confirming that it was the oxazolidine. Aldehyde contaminants can transform the drug of interest and may result in misidentification of a compound not originally present in specimens. Therefore, chemicals used in analyses should be of the highest available purity, and a multianalytical approach should be adopted to maintain a high degree of quality assurance.