Study On Process Optimization And Quality Standard Of Abiraterone

Prostate cancer is the most common malignant tumor of the male reproductive organs and the incidence of prostate cancer is increasing significantly.ZYTIGA（abiraterone）is an indispensable and extremely important drug,abiraterone has a short history on the market in China and some areas where the research is lacking.The synthesis and preparation process were further optimized and the correlation analysis of its quality was also conducted,because abiraterone is a lipophilic substance with very low solubility,cyclodextrin inclusion technology was used to increase the solubility of abiraterone,so that it can play a stable role.Finally,the cytotoxic MTT test is done to verify the antitumor effect of the inclusion complex of abiraterone-2-HP-β-CD.The main research contents are as follows:1.In this study,the synthesis route of abiraterone API was further optimized,the material ratio between reactions was studied and other important conditions were screened,the cost of synthetic API was reduced and the reaction time was shortened,and the target product was finally obtained.2.In this study,the solubility of abirateroneβ-cyclodextrin was detected by the phase solubility method.It was proved that the cyclodextrin could encapsulate abiraterone and increase the solubility of abiraterone.The inclusion complex of abiraterone was obtained.3.The study contained the determination of API content and stability of abiraterone API.The quantitative and qualitative control of abiraterone content was achieved by establishing HPLC method.The linear equation of abiraterone content was y=555441x-371745,R2=0.9991,indicating a good linear relationship between the mass concentration of abiraterone and 5.2μg·ml^-1-83μg·ml^-1,and the limits of detection and quantification of abiraterone were0.17μg·ml^-1and 0.42μg·ml^-1.4.MTT assay was used to detect the inhibitory effect of abiraterone and its inclusion compound on the proliferation of mouse RM-1 cells in the same culture time,and both of them showed a good inhibitory effect on the proliferation of mouse RM-1 cells in a concentration-dependent manner.