Quality Studies For Saxagliptin Raw Materials

Saxagliptin,a new kind of dipeptidyl peptidaseⅣinhibitors,is a novel drug treating diabetes.The therapeutic effect is significant,and the research of the saxagliptin is very important for patients,families and society.In this paper,the quality study of the saxagliptin raw materials had been completed,the quality standard was also formulated.We have carried on comprehensive quality control from synthetic process to the final product of saxagliptin.In this study,the control of key intermediate of saxagliptin was described,and the quality standards have been determined.The saxagliptin raw materials were researched too.The characters of them were investigated.UV and IR spectrophotometry,and High Performance Liquid Chromatography(HPLC)methods were respectively established to identify them.The content,related substances,moisture,residue on ignition,heavy metals and other projects were checked.Finally,the stability of saxagliptin was also researched.These results were symbolized pharmacopoeia and related quality standards.In this study,efficient HPLC methods were developed for quality control of the related substances of intermediate-1 and intermediate-4.The internal control standards were also formulated.Methodology validation were performed for these new established tests.Simple and efficient HPLC methods were developed for quality control of the related substances and the enantiomer.Thermo C18 column was used with the mobile phase of gradient elution,and the flow rate was 1.0 ml/min,at the detection wavelength of 210 nm.The column temperature was 35°C and the injection volume was 10μl.This method was used to detect Saxagliptin and the impurities 1,2,3,4,5 6,7,8,and 9.The mobile phase was hexane:iso-propanol:diethylamine=15:85:0.05,the flow rate was 1.5 ml/min,and others were the same as the first one.This method was used to detect the enantiomer.These results showed that the separation of saxagliptin peak and impurities peaks were respectively greater than 1.5,which the determination of related substances were not interfered by blank solvent.Good linearity,specificity,precision,durability and high degree of accuracy were detected in the test.Therefore,the methods can be used to control the related substances of saxagliptin.A simple,quick,and accurate HPLC method was adopted for the assay of saxagliptin raw materials.The chromatographic conditions were the same as the related substances.These results showed that the blank solvent did not interfere the determination of saxagliptin.The calibration curve of saxagliptin was linear in the concentration range of10.1μg/ml～201.8μg/ml and R~2=1.0000.The RSD was less than 2.0%of the precision,accuracy and stability test.Finally,the stability of saxagliptin of the raw materials was investigated.These results showed that there were no significant changes for the assay and the related substances of the three batches of saxagliptin raw materials in the accelerated conditions and long-term conditions.The quality standard of the saxagliptin was scientific and reliable,having the practical significance.