Development and validation of highly selective method for the determination of imatinib mesylate and dexketoprofen trometamol combination in three different media

Imatinib mesylate is a small molecule used in cancer therapy as a thyrosine kinase inhibitor. Dexketoprofen trometamol is a non-steroidal anti-inflammatory drug that has seen use in cancer therapy in combination with an anticancer drug to minimize tumor size and to reduce pain in patients. In the present study, imatinib mesylate and dexketoprofen trometamol were selected as potential model drugs to be used in combination. A new, simple and selective Ultra Performance Liquid Chromatography method was developed and validated to determine the drug substances in distilled water, in a pH 7.4 phosphate buffer and in Dulbecco’s Modified Eagle Medium. The proposed method was developed using a BEH C-18 column with isocratic elution. A mixture of methanol:acetonitrile (80:20, v/v) and pH 9.5, 0.05 M ammonium acetate were (70:30, v/v) used as a mobile phase. Detection was carried out with a flow rate of 0.3 mL/min, a column temperature of 30°C and an injection volume of 20 μL. The method was validated considering linearity, accuracy, precision, specificity, robustness, detection limit and quantitation limit values, and was found to be linear in a range from 0.05 to 20.0 μg/mL for the three different media.

甲磺酸伊马替尼（Imatinib Mesylate）是一种用于癌症治疗的小分子酪氨酸激酶抑制剂。右酮洛芬氨丁三醇（Dexketoprofen Trometamol）属于非甾体抗炎药，常与抗肿瘤药物联合应用于癌症治疗，以缩小肿瘤体积并缓解患者疼痛。本研究选用甲磺酸伊马替尼与右酮洛芬氨丁三醇作为联合给药的候选模型药物。本研究建立并验证了一种新颖、简便且选择性优异的超高效液相色谱法（Ultra Performance Liquid Chromatography），用于测定两种药物在蒸馏水、pH 7.4磷酸盐缓冲液以及达尔伯克改良伊格尔培养基（Dulbecco’s Modified Eagle Medium）中的含量。该方法采用BEH C-18色谱柱进行等度洗脱，流动相为体积比80:20的甲醇-乙腈混合液与体积比70:30的0.05 M乙酸铵缓冲液（pH 9.5）。检测时设置流速为0.3 mL/min，柱温30℃，进样体积20 μL。本方法通过线性、准确度、精密度、专属性、耐用性、检测限与定量限进行方法学验证，结果显示在三种测试介质中，两种药物在0.05~20.0 μg/mL的浓度范围内均呈现良好的线性关系。