Quality Studies For Clopidogrel Hydrogen Sulfate

In order to control the quality of clopidogrel hydrogen sulfate products and ensure the safety of medication,the related substances（impurity A,impurity B,impurity C）,residual solvents（acetone,acetonitrile,dichloromethane,ethyl acetate）and the assay of clopidogrel hydrogen sulfate were established for determination.1)Related substances:An HPLC method was established.The column Ultron ES-OVM（4.6×150 mm,5μm）was used in this method.The chromatographic conditions were:0.01mol.L^-1potassium dihydrogen phosphate-acetonitrile=78:22 was the mobile phase,the flow rate was 1.0 m L.min^-1,and the detection wavelength was 220 nm.The results showed that:Impurity A,impurity B,impurity C were well separated from clopidogrel hydrogen sulfate,and the detection limit of Impurity A,Impurity B,Impurity C were 0.009μg.m L^-1、0.049μg.m L^-1、0.636μg.m L^-1,the average recovery rates were between 98.0～102.0%,the precision RSD value was less than 2.0%.The method is simple,high sensitivity and high accuracy.It can be used for the detection of related substances of clopidogrel hydrogen sulfate.2)Residual solvent:GC chromatography was used with DMF as the solvent.The capillary column DA-624（60 m×0.25 mm,1.4μm）and FID detector were used.The column temperature was raised from 60℃（kept for 3 min）to 180℃（then kept for 8min）by program at the rate of 10℃·min^-1.The injector temperature was 200℃and the detector temperature was 200℃.The results showed that all four organic solvents were completely separated and had good linearity in the concentration range examined.The detection limit concentrations of acetone,acetonitrile,dichloromethane and ethyl acetate were 0.800μg.m L^-1,1.770μg.m L^-1、1.455μg.m L^-1、0.660μg.m L^-1.The average recovery rates were between 98.0～102.0%.The method is simple,high sensitivity and high accuracy,and can be used for the detection of residual solvent of clopidogrel hydrogen sulfate.3)Assay:A HPLC method for determination the assay of clopidogrel hydrogen sulfate,using Ultron ES-OVM（4.6×150m,5μm）chromatographic column.The chromatographic conditions were:0.01 mol.L^-1potassium dihydrogen phosphate:acetonitrile=78:22 was the mobile phase,the flow rate was 1.0 m L.min^-1,and the detection wavelength was at 220 nm.The results showed that clopidogrel hydrogen sulfate had good linearity in the concentration range of 0.0501 mg.m L^-1～0.2002mg.m L^-1（R²=0.9997）,the average recovery rate was 99.77%,and the precision RSD values were less than 2.0%.The quality standard for Charaters,Identification（infrared spectroscopy,ultraviolet-visible spectroscopy,high-performance liquid chromatography and sulfate identification）,Tests（related substances,residual solvents,p H value,loss on drying,heavy metals）and Assay of clopidogrel hydrogen sulfate was established.