抗脂肪肝新药IMH的差示扫描量热法纯度定值研究及不确定度评估  

Determination of purity of a new anti-fatty liver drug IMH by differential scanning calorimetry method and uncertainty evaluation

作　　者：邵会会 雷康璠 秦通 张文轩 吴松 杨庆云 SHAO Hui-hui;LEI Kang-fan;QIN Tong;ZHANG Wen-xuan;WU Song;YANG Qing-yun(State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medica,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,天然药物活性物质与功能国家重点实验室,北京100050

出　　处：《药学学报》2023年第3期767-772,共6页Acta Pharmaceutica Sinica

基　　金：中国医学科学院医学与健康科技创新工程项目(2021-I2M-1-028)。

摘　　要：建立差示扫描量热法(differential scanning calorimetry,DSC),测定脂肪肝治疗新药4,4′-二甲氧基-5,6,5′,6′-双(亚甲二氧基)-2′-吗啉亚甲基联苯-2-甲酸甲酯甲磺酸盐(简称IMH)的纯度。采用双因素无重复性方差分析,优化DSC实验参数为升温速率10℃·min^(-1),温度区间150~300℃,称样量范围2.0~4.1 mg,N2流速80 mL·min^(-1);该DSC方法验证的线性相关系数r=0.9998;精密度RSD(n=6)为0.03%;多批次IMH药物纯度测定结果的标准值及不确定度分别为(99.74±0.29)%、(99.91±0.28)%、(99.90±0.28)%、(99.81±0.28)%,包含因子K=2,置信概率P=0.95,其结果与质量平衡法测定结果基本一致。该DSC方法简便、快捷、准确,为IMH纯度定值提供新的方法,提高了IMH药物纯度测定的准确性和可靠性。The purity of 4,4′-dimethoxy-5,6,5′,6′-bis(methylenedioxy)-2′-morpholine methylenebiphenyl-2-methyl formate methanesulfonate(IMH),a new drug for fatty liver treatment,was determined through differential scanning calorimetry(DSC).Analysis of two-factor non repeatability method was performed in the investigation the effects of two factors(heating rate and sample weight)on purity determination.The DSC experimental parameters were optimized as follows:heating rate was 10℃·min^(-1),temperature range was 150-300℃,sample weight was 2.0-4.1 mg,and N2 flow rate was 80 mL·min^(-1).The linear correlation coefficient(r)of this DSC method was 0.9998.The RSD value(n=6)of precision was 0.03%.The standard value and uncertainty of the purity results of the multiple batches of IMH drugs were(99.74±0.29)%,(99.91±0.28)%,(99.90±0.28)%,and(99.81±0.28)%with inclusion factor(K)of 2 and confidence probability(P)of 0.95.The results were basically consistent with the results of the mass balance method.The DSC mehod is a simple,rapid and accurate method,and provides a new reference method for determining the purity of IMH drugs,improves the accuracy and reliability of purity determination.

关 键 词：抗脂肪肝药物 差示扫描量热法 纯度测定 不确定度 质量控制 

分 类 号：R917[医药卫生—药物分析学]