Szczepek W J, Kosmacińska B, Bielejewska A, Łuniewski W, Skarzyński M, Rozmarynowska D
Pharmaceutical Research Institute, Rydygiera 8, 01-793 Warsaw, Poland.
J Pharm Biomed Anal. 2007 Apr 11;43(5):1682-91. doi: 10.1016/j.jpba.2006.12.033. Epub 2007 Jan 12.
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.
本文研究了甲磺酸伊马替尼（ImM）在水解（中性、酸性、碱性）、氧化和光解条件下的分解情况。甲磺酸伊马替尼在中性条件下实际上是光稳定且稳定的。在酸性和碱性条件下的主要降解产物是化合物：4-甲基-N3-(4-吡啶-3-基-嘧啶-2-基)-苯-1,3-二胺（2）和4-(4-甲基-哌嗪-1-基甲基)-苯甲酸（3）。在氧化条件下的主要降解产物，即4-[(4-甲基-4-氧化-哌嗪-1-基)-甲基]-N-[4-甲基-3-(4-吡啶-3-基-嘧啶-2-基氨基)-苯基]-苯甲酰胺（6）、4-[(4-甲基-1-氧化-哌嗪-1-基)-甲基]-N-[4-甲基-3-(4-吡啶-3-基-嘧啶-2-基氨基)-苯基]-苯甲酰胺（7）和4-[(4-甲基-1,4-二氧化-哌嗪-1-基)-甲基]-N-[4-甲基-3-(4-吡啶-3-基-嘧啶-2-基氨基)-苯基]-苯甲酰胺（8），从反应混合物中分离出来，并通过高效液相色谱法（HPLC）、核磁共振氢谱（1H NMR）和质谱（MS）技术进行鉴定。在稳定性研究中，验证了所提出的高效液相色谱法用于控制样品纯度的适用性。
