Study On Dtermination Of Related Substances Of Prasugrel Hydrochloride By HPLC Method

Purpose: Establishing a HPLC method for determination of related substances of prasugrel hydrochloride.Method: Compared with the existing literature,and combined with the impurities of prasugrel hydrochloride in the company,the literature method can not separate and detecte all the impurities.Therefore,HPLC method is developed.Study the key parameters of HPLC chromatographic conditions,including wavelength selection,mobile phase selection,column selection,column temperature selection,and solvent selection for preparation sample solution,to determine the method of HPLC chromatographic conditions,and validate the test method.Results: Determination of related substances of prasugrel hydrochloride,the chromatographic column is Agilent ZORBAX SB-C8,250 mm×4.6 mm,5 ?m;Column temperature is 30?;Wavelength is 210 nm;Injection volume is 10 ?L;Mobile phase: A: 0.01 mol/L potassium dihydrogen phosphate,adjust pH = 3.0 with phosphoric acid,B: acetonitrile,gradient elution: 0-2 min,A proportion is 70%,2-16 min,A proportion is 70%-58%,16-30 min,A proportion is 58%-30%,30-40 min,A proportion is 30%,40-40.01 min,A proportion is 30%-70%,40.01-50 min,A proportion is 70%,the sample solution is prepared with acetonitrile.The seven impurities of Prasugrel hydrochloride can be effectively controlled with the test method,the resolution between prasugrel peak and its adjacent impurity peak is more than 2.0,the resolution between the known impurities is more than 2.0,the sensitivity of method is high,for minimum 0.001% of impurity could be detected,and recovery of accaracy is between 80% ~ 120%,meanwhile,the linearity and range is wide,and the precision is good.Test three batches of sample,the test results of PRG-1a,PRG-1c,PRG-2 and PRG-a are 0.21%(limit: 0.30%),0.04%(limit: 0.15%),0.29%(limit: 0.50%)and 0.05%(limit: 0.30%)separately,and PRG-1b(limit: 0.15%),PRG-4b(limit: 0.15%)and PRG-f(limit: 0.10%)are not detected,meet the requirement.Conclusion: the HPLC method is suitable for seven impurities detection of prasugrel hydrochloride,and these impurities are common in current process of prasugrel hydrochloride,so the research in this paper has a certain reference value in this area.Meanwhile,the method has been established the enterprise internal standard,which apply to the control of related substances in the product in enterprise.