Formation of an interfering substance, 3,4-dimethyl-5-phenyl-1,3-oxazolidine, during a pseudoephedrine urinalysis

During fatal aviation accident investigations, biosamples from the victims are submitted to the FAA Civil Aeromedical Institute (CAMI) for drug analys is. In the process of one such analysis by CAMI, an unknown substance was f ound ina urine sample. Simultaneous screening by thin layer chromatography (TLC) and gas chromatography/FID (GC/FLD) suggested the presence of pseudoe phedrine. A subsequent routine confirmation analysis of a separate urine al iquot by GC Fourier transform infrared (GC/FTIR) and GC mass spectrometry ( GC/MS) 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, a nd the molar mass was 12 atomic mass units (amu) more than that of pseudoep hedrine. A subsequent literature search suggested that ephedrine-like amine s react with aldehydes to form oxazolidines. Therefore, the 12-amu increase could be accounted for by condensation of pseudoephedrine with formaldehyd e. Since this aldehyde is present in various grades of methanol and ethyl a cetate, and these solvents were used during the solid-phase extraction, 3,4 -dimethyl-5-phenyl-1,3-oxazolidine was synthesized by using (+)-pseudoephed rine . HCl and formaldehyde. The analytical findings of the synthesized com pound were consistent with those of the unknown interfering substance, conf irming that it was the oxazolidine. Aldehyde contaminants in solvents or sp ecimens can transform drugs of interest and may result in misidentification of a compound originally present in specimens. Therefore, chemicals used i n analyses should be of the highest available purity, and a multi-analytica l approach should be adopted to maintain a high degree of quality assurance .