Process Research and Impurity Control Strategy for Obeticholic Acid, a Farnesoid X Receptor Agonist

被引：4
|
作者：
Feng, Wei-Dong [1 ]
Zhuo, Song-Ming [2 ]
Zhang, Fu-Li [1 ,3 ]
机构：
[1] Zhejiang Univ Technol, Collaborat Innovat Ctr Yangtze River Delta Reg Gr, 18 Chaowang Rd, Hangzhou 310032, Zhejiang, Peoples R China
[2] China Pharmaceut Univ, Dept Pharmaceut Engn, 24 Tongjiaxiang, Nanjing 210009, Jiangsu, Peoples R China
[3] China State Inst Pharmaceut Ind, Shanghai Inst Pharmaceut Ind, 285 Gebaini Rd, Shanghai 201203, Peoples R China
来源：
ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2019年 / 23卷 / 09期
关键词：
obeticholic acid; process; primary biliary cholangitis; nonalcoholic steatohepatitis;
D O I：
10.1021/acs.oprd.9b00252
中图分类号：
O69 [应用化学];
学科分类号：
081704 ;
摘要：
The process to obtain ICH-grade quality obeticholic acid (OCA) was improved, and the overall yield was 25.9%. The critical process parameters were established to reduce or avoid process-related impurities. The formation mechanisms, purge pathways, and control strategies for these impurities were also discussed for the first time. An high-performance liquid chromatography instrument utilizing the charged aerosol detection technique was applied for an impurity content assay in OCA for the first time. The developed process was robust and suitable for manufacturing scale-up.
引用
收藏
页码：1979 / 1989
页数：11
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