Organic Process Research and Development p. 919 - 925 (2019)
Update date:2022-08-10
Topics:
Mannam, Madhava Rao
Sankareswaran, Srimurugan
Gaddam, Venugopal Reddy
Natarajan, Senthilkumar
Kottapalli, Rajasekhara Prasad
Kumar, Pramod
A new process-related impurity of ezetimibe was identified and characterized. The impurity is critical and common to most of the manufacturing routes of ezetimibe. Structural characterization using HMBC indicated the presence of a six-membered ring rather than a nine-membered ring as proposed by the innovator of ezetimibe. Prominently, the existing pharmacopoeial methods for ezetimibe are not capable of detecting this impurity. A control strategy was established by appropriate process control that is capable of purging the impurity to levels comfortably below the regulatory requirement. The formation of the diastereomer impurity during the demonstration of a scale-up batch under the optimized conditions is attributed to epimerization of ezetimibe induced by thermal degradation of the silylating agent.
View MoreTaizhou Crene Biotechnology co.ltd
Contact:86-576-88813233 88205808
Address:Economic Developed Zone of Taizhou Zhejiang China
Contact:+86-633-8332928
Address:No.1,Huanghai Yilu.Rizhao,Shandong
Hangzhou Share Chemical Co., Ltd
Contact:+86-57187093700
Address:Hang Xing Road
qingdao goldenchem imp and exp co.,ltd.
Contact:532-55579246
Address:no.62 ,haier road laoshan distirct
Contact:+49-4101-3053-0
Address:Waldhofstrasse 14 ,25474 Ellerbek Germany
Doi:10.1134/S1070363218080170
(2018)Doi:10.1021/jo00436a021
(1977)Doi:10.1002/lipi.19610630702
()Doi:10.1080/10426509708031588
(1997)Doi:10.1002/ardp.19773100302
(1977)Doi:10.1016/j.apcata.2014.10.022
(2015)