Studies On The Synthesis And Quality Research Of Rabeprazole Sodium

In recent years, proton pump inhibitors(PPI) has become the drug of choice for the treatment of gastric acid related disease. Rabeprazole sodium is omeprazole, lansoprazole, pantoprazole listed after the fourth proton pump inhibitor. Because of its high biological availability, quick, effective and long-time in acid suppression, rabeprazole sodium receives much concern and has a wide application and a huge potential market. The paper is mainly on the synthesis and quality of rabeprazole sodium. The synthesis process features good repetitiveness, contorllable quality and low cost. An effective method is established to control the quality of this medicine, which introduced reliable technical parameters for production.Rabeprazole sodium was prepared form 2-mercaptobenzimidazole and 2-(hydroxymethyl)-4-methoxypropoxy-3-methylpyriding via condensation under alkaline conditions, oxidation with 3-chloroperoxybenzoic acid, and salt formation according to the reported synthetic methods.In this study, the structure of synthetic compound was conformed by UV, IR, NMR along with element analysis, thermal analysis and X-ray diffraction (XRD). The results showed that the structure of the compound was completely in conformity with that of the control substance.Quality control method of rabeprazole sodium was studied comprehensively in this paper. PR-HPLC was developed for durg-related impurities in raw drugs. Zorbax SB-C18 column (4.6×250mm i.d.5μm) with UV detection at 284 nm, and the mobile phase consisted of methyl alcohol, 50mmol·L-1 of phosphoric solution (60:40, adjusted to pH7.0) were used. The result of experimentation showed that this method had a good specificity. And there is a good linear relationship in range of rabeprazole sodium 0.2～4.0μg/ml, and the repeated tests RSD is 0.24%(n=6), the limit of detection (LOD) of this method is 1.0×10-11 and the limit of quantification (LOQ) is 4.0×10-11. Eight kinds of organic residual solvent (such as methanol, dichloromethane, ethyl acetate, et al) were detected and made limit standards using Static Headspace Gas Chromatography Method (DM-624 Capillary Column:30m×530μm×3.0μm, stationary phase:6% biseyanopropyl-94% polycyanopropylphenyl siloxane, flame ionization detector(FID),nitrogen as carrier gas). The method is simple, accurate and suitable for the quality control for rabeprazole sodium.In order to observe the stability of rabeprazole sodium, accelaeraed tests at high temperature, high humidity and under strong light and long-term testing at indoor temperature were carried out. Results showed that the moisture absorption of rabeprazole sodium was serious, the stability of which was very good under packaging, shady and dry condition. The expiry date of rabeprazole sodium can be determined by one year temporarily. The storage conditions are keeping away form light, airtight and storing at cool place.