抗肺癌新型化合物TPX-0005有关物质检测方法的建立与验证  

Establishment and validation of the method for the detection of related substances in the new anti-lung cancer compound TPX-0005

作　　者：蔡亮亮 范义凤[1] 吴雯仪 徐新[1] 陈伯华[1] CAI Liang-liang;FAN Yi-feng;WU Wen-yi;XU Xin;CHEN Bo-hua(Department of Pharmacy,Affiliated Hospital of Nantong University,Nantong 226001,China;Sinopharm holding Nantong Co.,Ltd,Nantong 226001,China)

机构地区：[1]南通大学附属医院药学部,南通226001 [2]国药控股南通有限公司,南通226001

出　　处：《药物分析杂志》2021年第5期846-851,共6页Chinese Journal of Pharmaceutical Analysis

基　　金：国家自然科学基金项目(81900528);江苏省博士后科研资助计划项目(2020Z435);南通市市级科技计划项目(MSZ18107);南通市药学会-常州四药医院药学科研基金项目(ntyx1806)。

摘　　要：目的:建立抗肺癌新型化合物TPX-0005有关物质检测的高效液相色谱法,为TPX-0005的质量控制提供实验依据。方法:采用Agilent HC-C18(4.6 mm×150 mm,5μm)色谱柱,流动相0.1%甲酸水溶液(A)-乙腈(B),梯度洗脱(0~2 min,30%B;2~30 min,30%B→50%B;30~35 min,50%B→70%B;35~36 min,70%B→30%B;36~45 min,30%B),检测波长230 nm,柱温35℃,流速1.0 mL·min^(-1)。结果:TPX-0005主峰与其相邻杂质峰之间的分离度大于1.5,其他杂质峰之间的分离度大于1.4;质量浓度在0.1~20.2μg·mL^(-1)范围内,与峰面积呈现良好的线性关系(r=0.9992);检测下限、定量下限分别为0.03、0.08μg·mL^(-1)。结论:该方法适合TPX-0005的有关物质的测定,可为TPX-0005的后续研究与开发提供有价值的参考。Objective:To establish an HPLC method for the analysis of related substances in TPX-0005,a new anti-lung cancer compound,and to provide experimental basis for the quality control of TPX-0005.Methods:The Agilent HC-C18 column(4.6 mm×150 mm,5μm)was used as the chromatographic column with the mobile phase consisting of 0.1%formic acid-water solution(A)and acetonitrile(B)in gradient elution model.The gradient elution procedure was as follows:0-2 min,30%B;2-30 min,30%B→50%B;30-35 min,50%B→70%B;35-36 min,70%B→30%B;36-45 min,30%B.The detection wavelength was 230 nm,the column temperature was 35℃and the flow rate was 1.0 mL·min^(-1).Results:The resolution between the main peak of TPX-0005 and its adjacent impurity peaks was greater than 1.5,and that of other impurities was greater than 1.4.There was a good linear relationship between the concentration and the peak area in the range of 0.1-2.2μg·mL^(-1)(r=0.9992).The concentration of detection limit and quantitative limit were 0.03μg·mL^(-1)and 0.08μg·m L^(-1)respectively.Conclusion:The method is suitable for the determination of related substances in TPX-0005,and can provide valuable reference for the follow-up research and development of TPX-0005.

关 键 词：肺癌 新型化合物 TPX-0005 强降解试验 有关物质 高效液相色谱法 

分 类 号：R917[医药卫生—药物分析学]