The Study On Chromatographic Analysis Methods Of Canagliflozin And Dapagliflozin As Well As Their Intermediates

Canagliflozin and Dapagliflozin were new antidiabetic drugs of SGLT2, primarily for the treatment of type 2 diabetes. Recent years have been listed in the foreign markets, but they are not listed in the domestic market. Although methods to detect the purity of Active Pharmaceutical Ingredients (API) have been reported, these methods were not systematic or reliable. Besides methods to analysis and separate these APIs and their intermediates have not been reported. In this paper we developed HPLC methods to detect purity and content of Canagliflozin and Dapagliflozin, to separate their intermediates, then validated these methods systematically. This paper has provided references to Canagliflozin and Dapagliflozin for further development, production, and usage in our country. The paper including following three parts:The first part introduced diabetes and sodium dependent glucose transporter (SGLT)2 inhibitor, viewed the application of HPLC in medicine industry and current situation of analysis studies about Canagliflozin and Dapagliflozin.In the second part methods to detect purity, content and related substances of Canagliflozin were established.Firstly, a method to detect purity and content of Canagliflozin was developed. Mobile phase was composed by ACN and H2O with gradient elution, then we validated the method. The results showed that this method had a good linear relationship, with linear regression equation of y= 0.4477x+0.8116(R2=0.9998). The results of accurancy and precision experiments met requirments of Chinese Pharmacopoeia. Then we investigaed its related substances-important intermediats ?-1 and ?-3. The linear regression equations of ?-1 and ?-3 respectively were y=1.1949x-0.053(R2=1), y=0.1958x-0.0182 (R2=0.9998). The results of accurancy and precision met requirments of Chinese Pharmacopoeia.Besides, we also developed a method to separate Canagliflozin and its a-configuration isomer. Chromatographic parameters such as mobile phase composition and type, temperature and flow rate were investigated to obtain the optimum separation. The optimized parameters were H2O-ACN=57%-43%(v/v),1.0 mL·min-1,30?. The validation results showed:the linear regression equations of Canagliflozin and its a-configuration isomer respectively were y= 5.3725x+8.3601 (R2=0.9993) and y=19.657x-15.42(R2=0.9998). The limit of quantitation was 0.37?g·mL-1, the limit of detection was 0.04?g·mL-1. The results of accurancy and precision experiments met the requirments of Chinese Pharmacopoeia. In the third part methods to detect purity, content and related substances of Dapagliflozin were established.Like wise. Firstly, a method to detect purity and content of Dapagliflozin was developed. Mobile phase was composed by ACN and H2O with gradient elution, then we validated the method. The results showed that this method had a good linear relationship, with linear regression equation of y=0.42x+0.6088 (R2=0.9993). The results of accurancy and precision expeiments met requirments of Chinese Pharmacopoeia. Then we investigaed important intermediats ?-1 and ?-3. The linear regression equations of ?-1 and ?-3 respectively were y=0.6987x+0.1276 (R2=0.9996), y=0.2724x+0.2929 (R2=0.9994). The results of accurancy and precision expeiments met requirments of Chinese Pharmacopoeia.Besides, we also developed a method to separate Dapagliflozin and its a-configuration isomer. Chromatographic parameters such as mobile phase composition and type, temperature and flow rate were investigated to obtain the optimum separation. The optimized parameters were H2O-ACN=63%-37%(v/v),1.0 mL·min-1,30?. The validation results showed:the linear regression equations of Dapagliflozin and its a-configuration isomer respectively were y= 0.5618x+0.0191 (R2=0.9999) and y=0.7044x-0.0048 (R2=0.9999). The limit of quantitation was 0.25?g·mL-1, and the limit of detection was 0.025?g·mL1. The results of accurancy and precision expeiments met the requirments of Chinese Pharmacopoeia.