Study On The Quality Control Method And Standard Of Ipragliflozin Based On Synthesis Process

Ipragliflozin is a new,powerful and highly selective sodium-glucose cotransporter II inhibitor,which can achieve fasting and postprandial glucose reduction by enhancing urinary glucose excretion in patients with type 2 diabetes.Efficacy and small side effects.It went on sale in Japan in 2014,no related quality standards for this product.This thesis is mainly based on the new drug development requirements and related principles,based on the new synthetic process,quality research,determine the quality control methods,and establish internal control standards.Firstly,based on the new synthetic method of Ipragliflozin developed in the early stage of the laboratory,self-made Ipragliflozin and research on the appearance,solubility,melting point and crystal form of the self-made products;determine the identification method;determine the moisture,heavy metals,and burning Residues and established residual solvent methods were used to determine the residual amounts ofmethanol,ethanol,acetonitrile,isopropyl ether,dichloromethane,ethyl acetate,tetrahydrofuran,n-hexane,and toluene 9 solvents.Secondly,the impurity of this product is researched,the assignment of each impurity is determined according to the synthesis process and the detection of the final product,and the largest impurity in the final product is the isomer impurity(impurity h)of this product by LC-MS method;By gradient elution through a silica gel column,the unknown impurities f and impurity g by-products were separated and prepared,and the unknown impurities f and impurity g were analyzed by NMR,IR and LC-MS methods,the impurity f is 1-fluoro-9H-thioxanthen-4-yl 4-vinylbenzoate,the impurity g is 6-(3-(benzothiophene-2-ylmethyl)-4-fluorophenyl)-2-methyltetrahydro-2H-pyran-3,4-diol;Then through the analysis and tracking of known impurities and unknown impurities to establish the impurity spectrum of this product.Based on the differences in the nature and structure of the impurities,the detection methods I and II of the related substances were developed,namely high-performance liquid chromatography and gas chromatography,and the methods were verified to be exclusive,accurate,and reliable.Based on the related substances and literature analysis methods of this product,the standard reference material of Ipragliflozin L-proline was standardized,and the HPLC method with isocratic elution of acetonitrile and water was established to analyze Content determination.Ipragliflozin L-proline.Finally,ethanol,ethanol: water = 10: 1,and methanol were selected as the recrystallization solvents.By analyzing the melting points,infrared spectra,and XRD results of the three samples,the infrared spectrum characteristic absorption peaks,melting points,and The characteristic peaks at different diffraction angles are the same,and the diffraction angles 2? are8.93°,9.62°,12.33°,16.48°,17.44°,18.67°,20.53°,21.43°.