RP-HPLC法测定埃索美拉唑钠的有关物质

目的: 建立RP-HPLC法测定埃索美拉唑钠有关物质的方法。 方法: 采用Venusil XBP C₁₈(L)色谱柱(250 mm×4.6 mm,5 μm),流动相采用乙腈-磷酸盐缓冲液(pH 7.6)-水梯度洗脱,流速为0.8 mL·min^-1,柱温为30 ℃,检测波长为302 nm。 结果: 在选定的色谱条件下,主成分能与各杂质之间分离良好,5-甲氧基-2-巯基苯并咪唑、奥美拉唑砜N-氧化物、奥美拉唑砜、埃索美拉唑钠及奥美拉唑硫醚浓度分别在3.99~29.94 μg·mL^-1(r=0.9998)、4.06~30.45 μg·mL^-1(r=0.9999)、2.46~18.42 μg·mL^-1(r=0.9998)、3.96~29.67 μg·mL^-1(r=0.9994)、4.08~31.32 μg·mL^-1(r=0.9998)范围内与峰面积呈良好的线性关系。上述化合物的平均回收率和RSD分别为99.5%、0.6%;99.1%、0.3%;99.0%、0.6%;99.2%、0.9%、99.0%、0.7%(n＝9)。 结论: 本方法可用于检测埃索美拉唑钠产品质量。

Objective: To establish a RP-HPLC method for the determination of related substances of esomeprazole sodium. Methods: The determination was performed on a Venusil XBP C₁₈(L)column(250 mm×4.6 mm,5 μm),with a mobile phase consisting of a mixture of acetonitrile and phosphate buffer(pH 7.6)by gradient elution.The column temperature was set at 30 ℃ with a flow rate of 0.8 mL·min^-1 and the detective wavelength was 302 nm. Results: Related substances were completely separated from the main constituent.The calibration curves for 5-methoxy-2- mercaptobenzimidazole,omeprazole sulfone N-oxide, omeprazole sulfone,esomeprazole sodium and omeprazole sulfide revealed good linearities over the ranges of 3.99-29.94 μg·mL^-1(r=0.9998),4.06-30.45 μg·mL^-1(r=0.9999),2.46-18.42 μg·mL^-1(r=0.9998),3.96-29.67 μg·mL^-1(r=0.9994),4.08-31.32 μg·mL^-1(r=0.9998),respectively.The recoveries of the above compounds were 99.5% with RSD of 0.6%,99.1% with RSD of 0.3%,99.0% with RSD of 0.6%,99.2% with RSD of 0.9%,99.0% with RSD of 0.7%,respectively. Conclusion: The method can be used for testing the product quality of esomeprazole sodium.

1 DONG Hua(董华).Advances in the pharmacology research of esomeprazole(埃索美拉唑药理研究进展).Shandong Med J(山东医药),2007,47(16):97
2 WANG Jing(王静),HOU Xiao-hua(侯晓华).Advances in the clinical applications of esomeprazole(埃索美拉唑的临床应用进展).Chin J Gastroenterol(胃肠病学),2003,8(2):125
3 ZHANG Hui-min(张晖敏),MIAO Ying-lei(缪应雷).Advances in the clinical applications of esomeprazole(埃索美拉唑的临床应用新进展).World Chin J Digestol(世界华人消化杂志),2009,17(20):2064
4 GU Tong-jin(顾同进),ZHU Yue(竺越).The new drug of PPI-esomeprazole(质子泵抑制剂族的新药—埃索美拉唑).Chin J Clin Pharm(中国临床药学杂志),2006,15(2):73
5 YANG Li(杨丽),YAN Bao-xia(严宝霞).Pharmacokinetics of esome prazole(埃索美拉唑的药动学).Chin J New Drugs(中国新药杂志),2004,13(5):398
6 HU Xiao(胡晓),TANG Xiao-hai(唐小海),XIE Yong-mei(谢永美),et al.Determination of S-omeprazole sodium and the related substances by RP-HPLC(RP-HPLC法测定S-奥美拉唑钠及其有关物质的含量).J China Pharm(中国药房),2009,20(22):1744
7 TAO Qiao-feng(陶巧凤),CHEN Xue-fan(陈雪帆),JIN Xin(金鑫),et al.Determination of related substance in omeprazole and its enteric-coated capsules(奥美拉唑原料及其肠溶胶囊有关物质检查方法的研究).Chin J Pharm Anal(药物分析杂志),2005,25(5):576
8 QIN Hai-chun(秦海春).Investigating the clinical efficacy and safety of gastroesophageal reflux esomeprazole(埃索美拉唑治疗胃食管反流病疗效观察).J China Mod Doctor(中国现代医生),2012,50(2):54
9 TAN Zhuang-chen(谭壮忱).Curative survey of flowing-back esophagitis between esomeprazole and omeprazole(埃索美拉唑与奥美拉唑治疗反流性食管炎的疗效观察).Chin J Med Guide(中国医药导刊),2008,10(3):416
10 GU Wei-jun(顾维钧),SUI Qiang(隋强),WANG Xiao-mei(王小妹),et al.Graphical synthetic routes of(埃索美拉唑合成路线图解).Chin J Pharm(中国医药工业杂志),2011,42(4):308
11 ZHAO Shan-shan(赵姗姗),LU Hua(卢华),ZHANG Yue-cheng(张月成),et al.Application of D(-)-di-pyridylmethyl tartaric acid amide in the synthesis of esomeprazole through asymmetric oxidation(D-(-)二吡啶甲基酒石酸酰胺在不对称氧化合成埃索美拉唑中的应用).J Mol Catal(分子催化),2012,26(1):46
12 LI Xie(李谢),DU You-guo(杜有国),ZONG Zai-wei(宗在伟),et al.Research of synthesis of omeprazole sodium(S-(-)-奥美拉唑钠的合成研究).Chem Ind Times(化工时刊),2009,23(2):35
13 HAO Ling-hua(郝玲花),LI Wei(李薇),WEI Jin-zhao(魏金钊),et al.Preparation of two impurities of omeprazole(奥美拉唑产品中二种杂质的制备).Chin J Pharm(中国医药工业杂志),2009,40(2):97