去氨加压素片有关物质测定方法分析  

Analysis of Determination Methods of Related Substances in Desmopressin Tablets

作　　者：孙悦[1] 胡馨月 张伟[1] 张慧[1] 李晶[1] 梁成罡[1] Sun Yue;Hu Xinyue;Zhang Wei;Zhang Hui;Li Jing;Liang Chenggang(National Institutes for Food and Drug Control,NMPA Key Laboratory for Quality Research and Evaluation of Chemical Drugs,Beijing 102629,China)

机构地区：[1]中国食品药品检定研究院,国家药品监督管理局化学药品质量研究与评价重点实验室,北京102629

出　　处：《中国药事》2023年第8期932-943,共12页Chinese Pharmaceutical Affairs

摘　　要：目的:去氨加压素片有关物质检测中一未知干扰物质影响有关物质检出和定量,不利于产品的质量可控,本文对该干扰物进行结构确证与来源归属,并优化有关物质测定方法以消除该未知物质干扰,为标准修订提供数据支持和参考。方法:采用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF/TOF MS)对未知干扰物质进行结构确证,通过改变色谱柱、流动相梯度等条件优化有关物质测定方法,对优化后方法进行方法学验证,并采用稳定性考察样品及多批次上市产品评价新的检测方法。结果:确证未知干扰物质为聚维酮K30,来源于制剂辅料;优化后的有关物质测定方法能够消除该辅料干扰,专属性、耐用性、精密度良好;去氨加压素在0.02μg·mL^(-1)至332μg·mL^(-1)浓度范围内呈良好的线性关系(r=0.9997);检出限和定量限分别为1 ng和2 ng。结论:该方法适用于去氨加压素片有关物质的测定,能够将辅料聚维酮K30充分洗脱,消除对有关物质测定的干扰。Objective:The structure confirmation and source attribution of an unknown interfering substance found in the related substance detection of desmopressin tablets were carried out,and the related substance method was optimized to eliminate the interference of the unknown substance,providing data support and reference for the revision of the standard.Methods:The structure of unknown interfering substance was confirmed using matrix assisted laser desorption ionization time of flight mass spectrometry(MALDI-TOF/TOF MS).The method for related substance was optimized by changing the chromatographic column,mobile phase gradient and other conditions,and the optimized method was validated by methodology,and the new detection method was evaluated by using stability test samples and multiple batches of marketed products.Results:It was confirmed that the unknown interfering substance was povidone K30,which is derived from the preparation excipients.The optimized method for determining related substance could eliminate the interference of the excipients,with good specificity,durability and precision.There was a good linear relationship(r=0.9997) for desmopressin at the concentration range of 0.02 μg·mL~(-1) to 332 μg·mL~(-1).The detection limit and quantification limit were 1 ng and 2ng,respectively.Conclusion:The method is suitable for the determination of related substances in desmopressin tablets,and can fully elute the excipient povidone K30 to eliminate the interference to the determination of related substance.

关 键 词：去氨加压素片 未知干扰物质 有关物质 聚维酮K30 基质辅助激光解吸电离飞行时间质谱 

分 类 号：R917[医药卫生—药物分析学]