The Synthesis And Quality Detection Of Abiraterone Acetate

This article confirms the synthesis process of abiraterone acetate, and optimizes the synthesis process. First, the 4-Pyridylboronic acid replaced the diethyl(3-pyridyl)borane, the 4-Pyridylboronic acid is cheap and easy to purchase. Next, the nitrogen atom of abiraterone with the acid to produce a salt, select a appropriate solvent to purify the salt, then dissociate the salt, to get the pure abiraterone. The two improvements which reduces the production cost and solves the amplification production problems.To establish an HPLC method for the determination of related substances of abiraterone acetate, make an quantitative control for the impurities of abiraterone acetate. The linear ranges were 0.41～14.45 μg·mL-1 (r=0.9998) for impurity A,0.42～14.71 μg ·mL-1 (r=0.9995)for impurity B,0.40～13.94 μg·mL-1 (r=0.9996)for impurity C,0.45～15.74 μg · mL-1 (r=0.9999) for impurity D,0.39～13.79 μg·mL-1 (r=0.9995) for impurity E, 0.39～13.54 μg·mL-1 (r=0.9996) for impurity F, respectively. The average recoveries (n=9) of the six components were 98.14%,99.34%,99.65%,100.27%,86.21% and 97.64%, with RSDs of 2.91%,2.59%,1.99%,1.69%,0.91% and 3.68%(n=9), respectively. The detection limits was 0.04,0.09,0.03,0.07,0.02,0.12μg · mL-1.To establish an HPLC method for the concent determination of Abiraterone acetate, make an quantitative control for the concent determination of Abiraterone acetate. The linear ranges were 0.04～0.14 mg ·mL-1 (r=0.9999) for Abiraterone acetate. The average recoveries (n=9) was 100.18%, with RSDs of 1.37%(n=9). The detection limits was 1.6μg ·mL-1.To establish an GC method for the determination of residual solvent of Abiraterone acetate, make an quantitative control and qualitative control for the residual solvent of Abiraterone acetate. The linear ranges were 0.12～0.42 mg · mL-1 (r=0.9997)for methanol, 0.2～0.7 mg · mL-1 (r=0.9994) for ethyl alcohol,0.2～0.7 mg·mL-1 (r=0.9999) for isopropyl alcohol,0.03～0.11 mg·mL-1 (r=0.9992) for tetrahydrofuran,0.01～0.035 mg ·mL-1 (r=0.9994) for pyridine,0.2～0.7 mg·mL-1 (r=0.9995) for acetic acid,0.022～ 0.076 mg · mL-1 (r=0.9996) for 1-Methyl-2-pyrrolidinone, respectively. The average recoveries (n=9) of the seven components were 99.87%,100.15%,99.35%,99.19%, 100.77%,98.60% and 99.19%, with RSDs of 2.51%,1.67%,1.87%,3.11%,3.01%,1.83% and 1.65%(n=9), respectively. The detection limits was 15,17,17,5,3,19.1 and 6.5μg mL-1.Through the study on related substances methodology, concent determination methodology and the determination of residual solvent methodology of abiraterone acetate. Proved these methods were accurate,rapid,sensitive with high repeatability,which is more suitable for the determination of related substances of Abiraterone acetate.