Effects of polyol excipient stability during storage and use on the quality of biopharmaceutical formulations  

作　　者：Min-Fei Sun Jia-Ning Liao Zhen-Yi Jing Han Gao Bin-Bin Shen You-Fu Xu Wei-Jie Fang 

机构地区：[1]Institute of Drug Metabolism and Pharmaceutical Analysis,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou,310058,China [2]Hangzhou Institute of Innovative Medicine,Zhejiang University,Hangzhou Biopharm Town,Hangzhou,310016,China [3]Zhejiang Haisheng Pharmaceutical Inc.,Taizhou,Zhejiang,318000,China

出　　处：《Journal of Pharmaceutical Analysis》2022年第5期774-782,共9页药物分析学报（英文版）

基　　金：generously provided by the National Natural Science Foundation of China(Grant No.:81741144);Ministry of Science and Technology of China(Grant No.:2018ZX09J18107-002).

摘　　要：Biopharmaceuticals are formulated using a variety of excipients to maintain their storage stability.However,some excipients are prone to degradation during repeated use and/or improper storage,and the impurities generated by their degradation are easily overlooked by end users and are usually not strictly monitored,affecting the stability of biopharmaceuticals.In this study,we evaluated the degradation profile of polyol excipient glycerol during repeated use and improper storage and identified an unprecedented cyclic ketal impurity using gas chromatography with mass spectrometry(GC-MS).The other polyol excipient,mannitol,was much more stable than glycerol.The effects of degraded glycerol and mannitol on the stability of the model biopharmaceutical pentapeptide,thymopentin,were also evaluated.The thymopentin content was only 66.4% in the thymopentin formulations with degraded glycerol,compared to 95.8% in other formulations after the stress test.Most glycerol impurities(i.e.,aldehydes and ketones)reacted with thymopentin,affecting the stability of thymopentin formulations.In conclusion,this work suggests that more attention should be paid to the quality changes of excipients during repeated use and storage.Additional testing of excipient stability under real or accelerated conditions by manufacturers would help avoid unexpected and painful results.

关 键 词：Excipient stability GC-MS GLYCEROL LC-MS/MS MANNITOL THYMOPENTIN 

分 类 号：R969.2[医药卫生—药理学]