Analysis of Amine Drugs Dissolved in Methanol by High‐Resolution Accurate Mass Gas Chromatography Mass Spectrometry, GC‐Orbitrap

The fragmentation pathways for amines dissolved in methanol (CH₃OH) or deuterated methanol (CD₃OD) have been investigated by high-resolution accurate mass gas chromatography mass spectrometry (HRAM-GCMS) or GC-Orbitrap. Primary and secondary amines used in this study were 1,3-dimethylamylamine (1,3-DMAA) and ephedrine hydrochloride (Eph), respectively. For isotopic labeling experiment, 1S, 2R (+) ephedrine-D₃ hydrochloride (D₃-Eph) was used. Under splitless injection mode at an inlet temperature of 250°C, formaldehyde and its deuterated form were generated from CH₃OH and CD₃OD, respectively. This was evidenced by the oxonium ions generated from each solvent. When 1,3-DMAA was dissolved in CH₃OH or CD₃OD, distinct separation between the unreacted amine and condensation product fragments was observed, specifically methylene-imine (M + 12) and deuteromethylene-imine (M + 14) artifacts. More complex condensation patterns for Eph and D₃-Eph were observed, attributed to the labile hydrogen/deuterium exchange and gradual deuteration from CH₃OH to CD₃OD. The fragmentation pathways were supported by the presence of oxazolidine intermediates before forming smaller condensation product fragments. Despite their close retention time and mass, the HRAM data distinguished the isobaric unreacted amine and condensation product fragments produced by Eph and D₃-Eph in the coeluting region.