Capillary gas chromatography using a γ-cyclodextrin for enantiomeric separation of methylamphetamine, its precursors and chloro intermediates after optimization of the derivatization reaction

• Problem of methylamphetamine seizures and consumption levels is presented.
• Three different commercially available acylating reagents were tested.
• Chemometric analysis of derivatization procedures was used.
• Two γ-cyclodextrin chiral stationary phases were tested.
• Chiral GC/MS method has been developed, optimized and validated.

The enantiomeric ratio of methylamphetamine (MAMP) is closely related to the optical activity of precursors and reagents used for the synthesis and this knowledge can provide useful information concerning the origins and synthetic methods used for illicit manufacture. The information can be utilized for regulation of the precursors and investigation of the manufacturing sources but this requires analytical procedures to determine purity of drug substances, impurity profiling and enantiomeric composition. In this study, a gas chromatography (GC) coupled with mass spectrometry (MS) method using a γ-cyclodextrin chiral stationary phase was developed and optimized for the simultaneous enantiomeric separations of MAMP and its common precursors, ephedrine, and pseudoephedrine, as well as its chlorointermediates formed during MAMP synthesis by the Emde method, after derivatization with trifluoroacetic anhydride. The optimization was performed using multivariate statistics (cluster analysis and principal components analysis) in order to select and compare optimal experimental conditions. Under the optimized experimental conditions, the calculated calibration curves showed good linearity range up to 0.1 μg/mL for all tested analytes. The limits of detection were in the range of 0.002–0.008 μg/mL and the coefficient of variability was between 1.0 and 3.9%. The method has the advantage of achieving excellent precision under repeatability and reproducibility conditions while detection by MS allows for the identity of analytes to be confirmed in a single analysis. The method was therefore applied satisfactory to MAMP analysis.