title: Identification of imatinib mesylate degradation products obtained under stress conditions.
abstract: 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.
authors.affiliation: Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland.
authors.forename: W J
authors.initials: WJ
authors.lastname: Szczepek
authors.forename: B
authors.initials: B
authors.lastname: Kosmacińska
authors.forename: A
authors.initials: A
authors.lastname: Bielejewska
authors.forename: W
authors.initials: W
authors.lastname: Łuniewski
authors.forename: M
authors.initials: M
authors.lastname: Skarzyński
authors.forename: D
authors.initials: D
authors.lastname: Rozmarynowska
mesh_terms: D000970:Antineoplastic Agents / Q000032:analysis* / Q000737:chemistry*; D001549:Benzamides; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D000068877:Imatinib Mesylate; D013058:Mass Spectrometry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D010782:Photolysis; D010879:Piperazines / Q000032:analysis* / Q000737:chemistry*; D047428:Protein Kinase Inhibitors / Q000032:analysis* / Q000737:chemistry*; D011743:Pyrimidines / Q000032:analysis* / Q000737:chemistry*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D013314:Stress, Mechanical; D013696:Temperature; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014867:Water; D000068877:Imatinib Mesylate