阿嗪米特中潜在基因毒性杂质马来酰肼的含量测定  

Content Determination of Potential Genotoxic Impurity Maleic Hydrazide in Azintamide

作　　者：赵钰馨 孙秉喆 倪卫星 梁然植 狄斌[1,3,4] 苏梦翔 ZHAO Yuxin;SUN Bingzhe;NI Weixing;LIANG Ranzhi;DI Bin;SU Mengxiang(School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China;Yangzhou Yiyang Pharmaceutical Co.,Ltd.,Jiangsu Yangzhou 225600,China;Key Laboratory of Drug Quality Control and Pharmacovigilance(China Pharmaceutical University),Ministry of Education,Nanjing 210009,China;Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients,National Medical Products Administration,Nanjing 210009,China)

机构地区：[1]中国药科大学药学院,南京210009 [2]扬州一洋制药有限公司,江苏扬州225600 [3]药物质量与安全预警教育部重点实验室(中国药科大学),南京210009 [4]国家药品监督管理局药物制剂及辅料研究与评价重点实验室,南京210009

出　　处：《中国药房》2021年第18期2189-2193,共5页China Pharmacy

基　　金：国家自然科学基金资助项目(No.81872833)。

摘　　要：目的:建立阿嗪米特原料药中潜在基因毒性杂质马来酰肼含量测定的方法。方法:采用高效液相色谱-荧光检测器法。以Thermo Syncronis C18为色谱柱,以0.2 mol/L乙酸溶液-甲醇为流动相进行梯度洗脱;柱温为30℃;激发波长为315 nm,发射波长为389 nm;流速为1 m L/min;进样量为20μL。结果:空白溶剂和阿嗪米特均不干扰马来酰肼的测定;马来酰肼检测质量浓度的线性范围为19.5~300 ng/mL(r=0.9999);检测限为4.5 ng/mL,定量限为19.5 ng/mL;加样回收率为98.79%~103.76%(RSD均小于3.00%,n=9);精密度、稳定性(24 h)试验的RSD均不大于5.63%,且耐用性试验的RSD均小于2.00%(n=6)。3批阿嗪米特原料药中均未检出马来酰肼。结论:该方法专属性好、灵敏度高、定量准确,可用于阿嗪米特或其他基质中马来酰肼的痕量测定。OBJECTIVE:To establish a method for the content determination of potential genotoxic impurity maleic hydrazide in azintamide raw material.METHODS:HPLC-FLD method was adopted.The determination was performed on Thermo Syncronis C18 column with mobile phase consisted of 0.2 mol/L acetic acid-methanol(gradient elution).The column temperature was set at30℃,the excitation wavelength was 315 nm and emission wavelength was 389 nm.The flow rate was 1 m L/min,and the sample size was 20μL.RESULTS:The blank solvent and azintamide did not interfere with the determination of maleic hydrazide.The linear range of maleic hydrazide was 19.5-300 ng/mL(r=0.9999).The limit of detection was 4.5 ng/mL and the limit of quantification was 19.5 ng/mL.The recovery ranged from 98.79%to 103.76%(RSDs were lower than 3.00%,n=9).RSDs of precision and stability(24 h)tests were no more than 5.63%,and those of durability tests were less than 2.00%(n=6).Maleic hydrazide was not detected in 3 batches of azinamide raw material.CONCLUSIONS:The method is specific,sensitive and accurate.It can be used for the trace determination of maleic hydrazide in azintamide or other matrix.

关 键 词：马来酰肼 阿嗪米特原料药 高效液相色谱-荧光检测器法 基因毒性杂质 

分 类 号：R917[医药卫生—药物分析学]