Application of GC-EI-MS for the identification and investigation of positional isomer in primaquine, an antimalarial drug

A major impurity associated with primaquine drug samples obtained from European Pharmacopoeia (EP) and other commercial sources was detected and identified using HPLC, photo diode array (PDA), LC-MS/MS and gas chromatograph-electron impact-mass spectrometer (GC-EI-MS). PDA and LC-ESI-MS/MS data provided an evidence for it being isomeric in nature. However, spectral data obtained from the newly developed GC-EI-MS method has been utilised for structural elucidation and found to be conclusive to characterize this impurity as positional isomer, i.e. 8-(4-amino-4-methylbutyl amino)-6 methoxyquinoline. The structure of this impurity has been confirmed by its synthesis. Precursor of primaquine was also investigated using GC-EI-MS. The data obtained confirmed the origin of isomeric impurity in precursor. (c) 2005 Elsevier B.V. All rights reserved.