Research On The Quality Of Apixaban

Apixaban(Eliquis^TM)is one of new generation oral anticoagulant drug and is a direct highly selective reversible factor Xa inhibitor.It is indicated in the prevention of venous thromboembolism?VTE?after major orthopaedic surgery,prevention of stroke orsystemic embolism in patients with atrial fibrillation.As an efficient and secureanticoagulant agent with extensive clinical application,Apixaban has huge quantity\demands in international markets,which has the potential to become a blockbuster drug.Because no legal quality standards and analysis methods of levetiracetam can be provided in Pharmacopoeias of each country,this paper involves the comprehensive analysis methods and quality research on it by modem analysis technology according to approval requirements of new drug in our country.Including structure identification,quality control research and stability inspect,which ensures that the quality of Apixaban controllable and adequately reflects the properties and the quality changes.The main contents include:1,Chemistry structure was studied by the ¹³C-HNMR and Ms,et al.The all results prove that the sample's molecule structure is conformity with that of Apixaban structure.2,In the quality research,scientific experiments were established according to chemical structure characteristic and production-techniques of Apixaban.The study was emphasized on character,indentification,tests and assay.Physics and chemistry constants such as appearance,solubility,melting point were tested.HPLC methods were established for determination of Apixaban's content and related substances.This method is based on HPLC determination of apixaban by using Waters Xbridge Shield RP18 C-18 column?250mm×4.6 mm,5.0?m?with isocratic conditions and simple mobile phase containing:20mmol/L CH₃COONH₄ with 0.1%triethylamine?pH was adjusted to 5.0 by CH₃COOH?:acetonitrile?72:28,v/v?,at flow rate of 1 mL/min using UV detection at 280 nm.Residual of organic solvents were tested by capillary GC method.The analysis methods were studied and validated according to the ICH guidance,the methods were proved to be accurate and reliable with high selectivity,sensitivity and reproducibility,and were suitable for the quality control of Apixaban.3,According to the requirements of the ICH guidelines,the stability of different batches are inspected by influence factor test,accelerated test and long-term test.The results shown that each project has no obvious change,and the indicators conform to the requirements of the quality standard.