Dasatinib is a protein kinase inhibitor used for the treatment of chronic myelogenous leukemia and acute lymphoblastic leukemia. Dasatinib along with its six known organic impurities were separated using the reversed-phase high performance liquid chromatography with C18 column and mobile phases consisting of gradient mixture of 20 mM potassium phosphate buffer at pH 6.0 with 1-octanesulphonic acid sodium salt (0.1%, w/v), acetonitrile and ultrapure water. This method was successfully tested with liquid chromatography coupled mass-spectrometry to elucidate the chemical structure of newly formed degradation product of Dasatinib which was identified by comparing its retention time and mass-spectra with literature data. Stability-indicating characteristics of developed HPLC method was assessed using stress testing [5 N HCl at 90 °C/1 h, 5 N NaOH at 90 °C/1 h, H2O at 90 °C/1 h, 30% H2O2 (w/w) at 25 °C ± 5 °C/1 h, dry heat at 105 °C/24 h and UV (200 W h m−2) and fluorescent light (1.2 million lux-h)] and was validated as per ICH Q2(R1). For Dasatinib and its six impurities, the quantification limits, linearity and recoveries were found in range of 0.19–0.21 μg/mL, 0.2–3.0 μg mL−1 (R2 > 0.995) and 85.5–107.0%, respectively. The developed HPLC method will also suffice the suitability for impurity profiling and assay of Dasatinib in bulk drugs and pharmaceutical formulations.

中文翻译：

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使用 LC-MS 和稳定性指示 HPLC 方法分离和表征片剂剂型中达沙替尼的新强制降解产物

达沙替尼是一种蛋白激酶抑制剂，用于治疗慢性粒细胞白血病和急性淋巴细胞白血病。达沙替尼及其六种已知有机杂质使用反相高效液相色谱法与 C18 柱分离，流动相由 20 mM 磷酸钾缓冲液（pH 6.0）与 1-辛磺酸钠盐（0.1%，w /v)、乙腈和超纯水。该方法经液相色谱-质谱联用检测成功，阐明了达沙替尼新形成的降解产物的化学结构，通过将其保留时间和质谱与文献数据进行比较，鉴定了达沙替尼降​​解产物的化学结构。已开发的 HPLC 方法的稳定性指示特征使用压力测试 [5 N HCl 在 90 °C/1 小时，90 °C/1 h 下的 5 N NaOH，90 °C/1 h 下的 H2O，25 °C ± 5 °C/1 h 下的 30% H2O2 (w/w)，105 °C/24 h 下的干热和UV (200 W hm-2) 和荧光灯 (120 万勒克斯-小时)] 并根据 ICH Q2(R1) 进行验证。对于达沙替尼及其六种杂质，定量限、线性和回收率分别在 0.19–0.21 µg/mL、0.2–3.0 µg mL-1 (R2 > 0.995) 和 85.5–107.0% 的范围内。开发的 HPLC 方法也足以适用于原料药和药物制剂中达沙替尼的杂质分析和分析。分别为 21 μg/mL、0.2–3.0 μg mL-1 (R2 > 0.995) 和 85.5–107.0%。开发的 HPLC 方法也足以适用于原料药和药物制剂中达沙替尼的杂质分析和分析。分别为 21 μg/mL、0.2–3.0 μg mL-1 (R2 > 0.995) 和 85.5–107.0%。开发的 HPLC 方法也足以适用于原料药和药物制剂中达沙替尼的杂质分析和分析。