摘要
目的:对注射用胸腺法新中与胸腺法新主峰较难分离的杂质结构进行鉴定并测定7家企业样品中杂质的含量。方法:结合使用基质辅助激光解析飞行时间串联质谱(MALDI-TOF/TOF MS)和二维-超高效液相色谱-四级杆飞行时间质谱(2D-UPLC-Q-TOF)测定杂质分子量并对结构进行鉴定,同时采用与合成的杂质对照品通过保留时间比对进行结构确认,并且通过HPLC方法对杂质含量进行测定。结果:测得胸腺法新主峰前后5个杂质分别为3个异构体杂质([D-Ser1]-胸腺法新、[D-Asp15]-胸腺法新、[D-Asn28]-胸腺法新)、1个缺失肽杂质([Des-Ala3]-胸腺法新)和1个水解杂质([Asp28]-胸腺法新),杂质含量为0.1%~1.0%。结论:使用两种质谱技术对杂质结构进行鉴定,结果可靠,本研究为完善质量标准以及制定合理的杂质限度提供了依据。
Objective:To identify the structures and determine the contents of the impurities difficultly separated from thymalfasin in thymalfasin for injection.Methods:MALDI-TOF/TOF MS and 2 D-UPLC-Q-TOF were used to measure the molecular weights and identify the structures of the impurities.Impurity standards were used to confirm the structures of the impurities.HPLC was applied to determine the contents of the impurities.Results:Five impurities were identified and the structures were confirmed as the peptide with the right racemization of the first serine([D-Ser1]-thymalfasin),the peptide with the right racemization of the fifteenth asparagine([D-Asp15]-thymalfasin),the peptide with the right racemization of the last asparagines([D-Asn28]-thymalfasin),the peptide with desorption of the third alanine of thymalfasin([Des-Ala3]-thymalfasin)and the peptide with hydrolysis of the last asparagine to aspartic acid([Asp28]-thymalfasin).The contents of the impurities were within the range of 0.1%-1.0%.Conclusion:The impurity structures are identified by using two MS techniques,and the results are reliable.The results of impurity contents provide the basis for the optimization of quality standard and impurity limits.
作者
张颖
尹红锐
徐蓓菁
郑璐侠
邵泓
陈钢
Zhang Ying;Yin Hongrui;Xu Beijing;Zheng Luxia;Shao Hong;Chen Gang(Shanghai Institute for Food and Drug Control,Shanghai 201203,China)
出处
《中国药师》
CAS
2020年第7期1417-1422,共6页
China Pharmacist
