Identification of imatinib mesylate degradation products obtained under stress conditions

In this paper, the decomposition of imatinib mesylate (ImM) under hydrolytic (neutral, acidic, alkaline), oxidative and photolytic conditions was studied. The imatinib mesylate is practically photostable and stable under neutral conditions. The main degradation products under acidic and alkaline conditions are compounds: 4-methyl-N3-(4-pyridin-3-yl-pyrimidyn-2-yl)-benzene-1,3-diamine (2) and 4-(4-methyl-piperazin-1-ylmethyl)-benzoic acid (3). The main degradation products under oxidation conditions, i.e. 4-[(4-methyl-4-oxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide (6), 4-[(4-methyl-1-oxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide (7) and 4-[(4-methyl-1,4-dioxido-piperazin-1-yl)-methyl]-N-[4-methyl-3-(4-pyridin-3-yl-pyrimidin-2-ylamino)-phenyl]-benzamide (8), were isolated from the reaction mixtures and identified by the HPLC, 1H NMR and MS techniques. During stress study the suitability of the proposed HPLC method to control purity of the samples was verified.