Research On Quality Of Non-sterile API Omeprazole

Objective:Throμgh comparison and analysis the impurities introducted from the omeprazole synthesis technology, develop new test methods for residual solvents which is not apply in the US pharmacopoeia, and the impurities detection methods from synthetic route of the starting material 5-methoxy-2-mercapto-1H-benzimidazole which are not included in USP, EP and CP pharmacopoeia, in order to ensure the quality control of omeprazole finished product. Methods:This research is on the basis of manufacturing process of omeprazole API, analysis the solvents: acetone, methylene chloride, toluene, benzene and methanol used in the production process, to form the suitable analysis method for residual solvent, and verify this method from the specificity, system suitability, quantitative limit, detection limit, linear, accuracy, durability seven aspects. And to provide methods and basis for quality control of residual solvents in omeprazole; This study throμgh analysis the impurities introduced from the production process of starting material, contrast to find out two genotoxic impurities which were not included in pharmacopoeia but may be broμght into omeprazole API products and affect their quality. Form analysis method and verify the limit of the method from specificity, detection limit, etc aspects.Results:Throμgh analysis methods validation, prove that the specificity of testing method for residual solvents acetone, methylene chloride, toluene, benzene and methanol in this research is good, system applicability is well, quantitative limit and detection limit accord with requirements, linear is stability(R2>0.99482), accuracy is high(RSD< 10%), the precision of the same lab technicians at different times, different lab technicians and different batches chromatography columns are good(RSD<10%) and after change the balance time of the top empty bottle,flow of detector, and column temperature, respectively, the durability is good. These prove that the method is accurate and reliable; the specificity of two genotoxic impurities, detection limit accords with requirements. At last, refer the detection methods of omeprazole monograph in the United States pharmacopoeia, combined with the residual solvent testing method, two kinds of genotoxic impurities detecting method to test the appearance, identification, solution clarity, impurity F and G, loss on dry, residue on ignition, heavy metals, related substances, residual solvents and assay of three consecutive batches of omeprazole finished product. Conclusion:The results show that the residual solvent testing method which is developed in this research and the testing method of two genotoxic impurities are feasible, and can be daily used in quality control of omeprazole API production. This research provides theory basis for formulate of omeprazole quality standards and the optimization of follow-up process, and also has a certain reference value for the quality control study of omeprazole API.