Synthetic Process And Quality Study Of Abiraterone Acetate

Abiraterone acetate is a highly selective and irreversible inhibitor of CYP17.It was developed by Johnson & Johnson US and first approved by FDA in April 2011,four years later,Abiraterone acetate marketed in China in May 2015.So far,abiraterone acetate is the first choice of treating metastatic castration-resistant prostate cancer(mCRPC)and metastatic high-risk castration-sensitive prostate cancer(m CSPC).The purpose of this work is to develop commercial synthetic process of abiraterone acetate,and to establish analysis methods for quality evaluation and control.The candidate commercial synthetic process that optimized and improved base on some literature and patents synthetic route has been designed.Validation of the synthesis process has been performed on one pilot batch test,that got 3.4kg API successful.The structural elucidation has been satisfactorily demonstrated by elemental analysis,IR,UV,NMR,MS,TG,DSC,XRD and XRPD.Impurity profile of this process has been assessed and listed.For some impurity with alerting structure,an assessment of Structure-Activity Relationships that focuses on bacterial mutagenicity predictions has been performed.According to the above research,impurity control strategy has been established.And then,impurity and assay methods have been developed and adequately validated.The analysis results of the pilot API achieve aims and expectations.Stability studies were performed under ICH Q1 A recommended test conditions,including accelerated(6 months)and long term(up to 12 months)stability studies.There were no notable changes to parameters during this study.The statistical analysis of stability data shows that the proposed shelf life of abiraterone acetate is 24 months.The research results have some practical significance and can provide technical support and reference for abiraterone acetate commercial manufacture and quality control.