The conversion of ephedrine to methamphetamine and methamphetamine-like compounds during and prior to gas chromatographic/mass spectrometric analysis of CB and HFB derivatives

Abstract

Ephedrine and methamphetamine standards were separately derivatized with heptafluorobutyric anhydride (HFBA) and carbethoxyhexafluorobutyryl chloride (CB) and analyzed by full-scan gas chromatography/ion trap mass spectrometry with electron ionization (EI) and chemical ionization (CI). Using EI, a high-concentration ephedrine standard produced a total ion gas chromatogram containing several minor HFB derivatives in addition to ephedrine. One of these had the same retention time as the derivative of methamphetamine, while another eluted 3 s later. Both contained the same major mass fragmentation ions that could be erroneously used in targeted selected ion monitoring gas chromatographic/mass spectrometric analysis for methamphetamine. The full-scan EI and CI spectra showed that these derivatives were not methamphetamine. CI mass spectrometric studies of ephedrine scanning up to m/z 700 demonstrated that reaction with HFBA caused acylation of both the hydroxyl and secondary amino groups. The HFBA used in this study was contaminated with pentafluoropropionic anhydride and tri-fluoroacetic anhydride and produced mixtures of derivatives, some with retention times near or identical to that of methamphetamine. In contrast, CB derivatization of ephedrine produces a single methamphetamine-like compound that has the same retention time and mass spectra as methamphetamine, and is produced only when high gas chromatograph injector temperatures are used ( > 260°C). Collision-induced decomposition tandem mass spectrometric studies for the CB derivative verified that methamphetamine is produced from ephedrine at elevated GC injection port temperatures. In view of these findings, substance abuse testing for methamphetamine in urine must proceed with caution when ephedrine and other sympathomimetic amines are present. Definitive analyses can be accomplished by full-scan CI gas chromatographic/mass spectrometric analysis with HFB derivatives, or by lowering gas chromatograph injector temperatures with CB derivatives.