Synthesis And Quality Research Of Esomeprazole Sodium

Esomeprazole sodium((S)-Omeprazole sodium)is the first PPTs launched as single isomer,clinically used to relief GERD,reflux esophagitis,gastric ulcer,duodenal ulcer and other disorders related to digestive acids or used to cure helicobacter pylori in combination with other medicines.This paper studied its synthetic process and quality control.Thesynthetic process of esomeprazole sodium can be generalized as follows:After the chlorination,condensation,asymmetric oxidation and salinization of 4-Methoxy-3,5-dimethyl-2-hydroxymethylpyridine,esomeprazole sodium which can be used directly as medicine will be obtained.The most critical link in this process is the asymmetric oxidation of omeprazole sulfide.Focusing on this process,this paper selected diethyl D-tartrate and isopropyl titanateaschiral auxiliary,trimethylamine as basic catalyst,and CHP as oxidizer,so as to explore how the ratio of chiral auxiliary,amount of oxidizer,temperature of oxidation and the acceleration of oxidizer drops will influence the yield and purity of esomeprazole sodium.It was finally found out that the following conditions are most favorable:omeprazole sulfide,diethyl D-tartrate,isopropyl titanate and CHP should be added at the ratio of 1.0:0.4:0.2:1.1,reacting under the temperature of-5??0? and with the oxidizer dropped in within about 30 minutes.By utilizing this optimized technique,the yield of esomeprazole sodium reached about 90%while the content of related substances is lower than 0.5%.The content of antipodes is above 99.9%.The target product was proved to be esomeprazole sodium through structural identification,such as IR and MS.Besides,this paper validated themethods to analyze related substances of esomeprazole sodium and purity of antipodes.Through the validation,conditions to measure related substances can concluded as follows:TakeMicrospher(C18,3 ?m,4.6 X 100mm)as filler,ACN-pH7.6-PBS-water(10:10:80)as mobile phase A,and ACN-pH7.6-PBS-water(80:1:19)as mobile phase B.Gradientelutionwas conducted at a flow rate of 1.0ml/min,and UV detection was made under the wavelength of 302 nm.Through the validation,conditions to measure the purity of antipodes can be concluded as follows:Take CHIRALPAK-AGP(2.5?m,4.0×100mm)as filler,ACN-pH6.0-PBS(15:85)as mobile phase flowing at a rate of 0.6ml/min,UV detection was made under the wavelength of 302 nm.Through systematical analytical methods validation,it was found out that the method was specified,sensitive,precise,durable,systematically compatible and wide in linear range.