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 (CHOH) or deuterated methanol (CDOD) 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-D hydrochloride (D-Eph) was used. Under splitless injection mode at an inlet temperature of 250°C, formaldehyde and its deuterated form were generated from CHOH and CDOD, respectively. This was evidenced by the oxonium ions generated from each solvent. When 1,3-DMAA was dissolved in CHOH or CDOD, 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 D-Eph were observed, attributed to the labile hydrogen/deuterium exchange and gradual deuteration from CHOH to CDOD. 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 D-Eph in the coeluting region.