埃索美拉唑镁肠溶片的质量研究

发布时间：2019-02-13 20:41

【摘要】：埃索美拉唑镁是治疗酸相关疾病的药物,是第一个单一光学异构体的质子泵抑制剂。2003年,埃索美拉唑镁肠溶片在中国获得上市批准(商品名:耐信,Nexium),上市的埃索美拉唑镁肠溶片有20 mg和40 mg两种规格。本课题对方法学进行了再验证并对埃索美拉唑镁肠溶片进行了质量研究。通过实验,主要得出以下几个结论:本实验对埃索美拉唑镁肠溶片进行了质量研究,分别采用高效液相色谱法对其含量、溶出曲线、有关物质、异构体等进行了检测,结果均符合2015版《中国药典》艾司奥美拉唑镁肠溶片质量标准。有关物质测定色谱条件:色谱柱:Microspher C18(4.6 mm×100 mm,3μm);流动相A:水-pH7.6磷酸盐缓冲液(每1000 mL中含磷酸二氢钠0.0052 mol、磷酸氢二钠0.0135 mol)-乙腈(80:10:10),流动相B:乙腈-pH7.6磷酸盐缓冲液-水(80:1:19);进样体积:20μL;柱温:35℃;检测波长:302 nm。流速:1 mL/min。主药与有关物质D的分离度大于2.5。空白辅料不干扰有关物质的测定。埃索美拉唑镁及有关物质线性关系良好;该方法准确,简便,重复性好,可用于埃索美拉唑镁肠溶片的质量控制。含量、溶出曲线测定色谱条件:色谱柱:Aglient Microspher C18,3.0μm,4.6mm×100 mm;流动相:乙腈-pH7.3磷酸盐缓冲液-水(35:50:15);检测波长:302 nm;进样体积:20μL;流速:1 mL/min;柱温:40℃。主峰保留时间大于3.5 min。空白辅料不干扰含量、溶出样品的测定,专属性较好,回收率均在98%~102%之间,符合要求,该方法能够准确测定埃索美拉唑镁肠溶片含量和溶出度。对映异构体检测色谱条件:流动相:乙腈-磷酸盐缓冲液(pH6.0)-水(150:85:765);色谱柱:CHIRALAPK?AGP(100×4 mm,5μm);检测波长:302 nm;进样体积:20μL;流速:0.6 mL/min;柱温:25℃。该方法简便,准确,专属性好,能够准确测定R-奥美拉唑的含量。最后,对埃索美拉唑肠溶片稳定性进行了考察。影响因素实验、六个月的加速实验分别以肠溶片的外观性状、溶出度、含量等为考察指标。实验结果表明,埃索美拉唑镁肠溶片在高温、高湿条件下均不稳定,应采用防潮包装并且避免接触高温环境。由加速实验数据的变化趋势可知,自制片与参比制剂的含量、有关物质、溶出度变化趋势基本一致,均符合艾司奥美拉唑镁肠溶片质量标准,具有较好的稳定性。
[Abstract]:Esomeprazole magnesium is the first proton pump inhibitor of a single optical isomer to treat acid-related diseases. Esomeprazolium enteric-coated tablets were approved in China in 2003 (trade name:, Nexium),) Esomeprazole magnesium enteric-coated tablets are available in 20 mg and 40 mg specifications. The methodology was revalidated and the quality of esomeprazolium enteric-coated tablets was studied. The main conclusions are as follows: the quality of esomeprazole magnesium enteric-coated tablets was studied in this experiment. The contents, dissolution curves, related substances, isomers and so on were determined by HPLC. The results were in accordance with the quality standard of esomeprazole tablets in 2015 edition of Chinese Pharmacopoeia. Chromatographic conditions for the determination of related substances: Microspher C18 (4.6 mm 脳 100 mm,3 渭 m);) Mobile phase A: water pH7.6 phosphate buffer (containing 0.0052 mol, sodium dihydrogen phosphate 0.0135 mol per 1000 mL) -acetonitrile (80:10:10), Mobile phase B: acetonitrile-pH7.6 phosphate buffer solution-water (80:1:19); Injection volume: 20 渭 L; column temperature: 35 鈩，

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