Studies On Quality Of Esomeprazole Magnesium

Esomeprazole magnesium is the first single-isomer proton pump inhibitor (PPI) in the world. But the quality standards of its bulk drug or preparation have not recorded into Chinese Pharmacopoeia yet. This thesis studied the quality of esomeprazole magnesium overall deeply, and establish its quality standards. The results can be instruction for quality control and evaluations.Objective:To establish assay methods for esomeprazole magnesium, including characterization, identification, testing, residual solvents, related substance, enantiomer, and content determination. It is a great importance to establish the quality standards and lay a foundation of later research.Methods:In this thesis, the characteristics of esomeprazole magnesium were investigated through appearance, solubility, melting point and specific rotation; esomeprazole magnesium was identified by chemical method, UV spectrophotometry and infrared absorption spectrophotometry; Exam the moisture and the loss on drying; Loss on drying and crystal water were tested. Residual of organic solvents were tested by Headspace GC method at first time. A HPLC method was established for determination of the relevant substances, A LC-MS method was used to identify this substance according to chemical structure characteristic and Production-techniques of esomeprazole magnesium. A HPLC method was established for determination of the enantiomer in esomeprazole magnesium. Non-aqueous titration and a HPLC method were used for content determination,the above two methods were compared.Results:Appearance, solubilities melting-point and optical rotation of the raw medicine were inspected; Chemical indentification result met the standards, and absorption spectrum of infrared radiation matched the spectrum of elaboration product; Mass loss on105℃drying was less than1.0%; Moisture content was between7%and8%; Residual solvents, including methanol, ethanol, acetone, acetic ether, dichloromethane, methyl cyanides, were all conformed with the regulations, and no residual solvent were detected; Chromatogram conditions were defined, while HPLC conditions for related substances were as follows: C18column, detection wavelength280nm, flow rate1.0mL/min, mobile phase: phosphate buffer(adjusted to pH=7.6by phosphate acid)-acetonitrile, gradient elute. HPLC conditions for optical isomoers were:CHIRALPAK AD-H (4.6x250nm,5um) chiral HPLC column, flow rate1.OmL/min, detection wavelength302nm, mobile phase N-hexane-isopropanol (83:17). Examination were done in three samples by the conditions above, while the results of related substances were0.131%.0.146%$å'Œ0.153%, the optical isomoers0.109%,0.115%,0.117%; The content determination were done by nonaqueous titration and HPLC methods. The conditions of HPLC was same as related substances examinaiton except for an isocratic elute. The results of two methods were99.84%,99.88%,99.69%and100.8%,101.0%,99.8%respectly.Conclusion: Based on the chemical structure, physical and chemical properties of esomeprazole magnesium, the characteristics, identification, examination and content determination for esomeprazole magnesium were studied in this thesis. The proposed methods and conditions are feasible and accurate. Methods for determination of residual solvents are feasible and accurate. The results are qualified and coincident with the standard. The research establish quality standards preliminary, and provide an effective instruction for quality control and evaluations.