溴吡斯的明缓释微丸的质量控制研究
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摘要
目的:建立溴吡斯的明缓释微丸含量测定、有关物质及释放度检查方法。方法:采用HPLC法进行有关物质检查和含量测定,色谱柱为艾杰尔C_(18)(250 mm×4.6 mm; 5μm),流动相为0.1%庚烷磺酸钠溶液(含0.5%三乙胺,磷酸调节pH至3.0)-乙腈,流速1.0 ml·min~(-1),检验波长269 nm,柱温35℃,进样量20μl。释放度检查采用桨法,以水为介质,转速50 r·min~(-1),在0.5,1,2,3,4,6,8,10,12 h取样,用UV法在269 nm波长处测定吸光度,计算释放度。结果:有关物质采用梯度洗脱,溴吡斯的明主峰与杂质A、杂质B及其他杂质能有效分离,样品中杂质A与杂质B均不大于0.2%,总杂质不大于0.5%;含量测定采用等度洗脱,样品含量测定结果为(240.5±0.16) mg·g~(-1);缓释微丸在5种介质中释放曲线一致,样品在12 h内累计释放度均大于80%。结论:建立的有关物质检查方法专属性强、灵敏度高,含量测定及释放度测定方法重复性、准确度好,可用于溴吡斯的明缓释微丸的质量控制。
Objective: To establish methods for the content determination,related substances and dissolution of pyridostigmine bromides sustained-release pellets. Methods: The content and related substances were determined by HPLC. The column was Aeger C_(18) (250 mm×4.6 mm,5 μm),the mobile phase consisted of sodium heptane sulfonate-triethylamine (adjusting pH to 3.0 with phosphoric acid) and acetonitrile,the flow rate was 1.0 ml·min~(-1),the detection wavelength was 269 nm,the column temperature was 35 ℃ and the injection volume was 20 μl. A paddle method was adopted using water as the dissolution medium. Samples were withdrawn at 0.5,1,2,3,4,6,8,10 and 12 h and the release was measured at the wavelength of 269 nm using UV-Vis spectrophotometry. Results:Gradient elution was used in the related substance test,and the main peak could be effectively separated from those of impurity A,impurity B and the other impurities. The contents of impurity A and impurity B in the samples were not more than 0.2%,and the total content of the impurities was not more than 0.5%. Equivalent elution was used in the content determination,and the sample content was (240.5±0.16) mg·g~(-1). The release curve profiles of the pellets showed similarity in five dissolution media and the cumulative release of the sample was over 80% within 12 hours. Conclusion: The determination method for the related substances is highly specific and sensitive,the method for the content determination and drug release both have good reproducibility and accuracy,which can be used for the quality control of pyridostigmine bromides sustained-release pellets.
Objective: To establish methods for the content determination,related substances and dissolution of pyridostigmine bromides sustained-release pellets. Methods: The content and related substances were determined by HPLC. The column was Aeger C_(18) (250 mm×4.6 mm,5 μm),the mobile phase consisted of sodium heptane sulfonate-triethylamine (adjusting pH to 3.0 with phosphoric acid) and acetonitrile,the flow rate was 1.0 ml·min~(-1),the detection wavelength was 269 nm,the column temperature was 35 ℃ and the injection volume was 20 μl. A paddle method was adopted using water as the dissolution medium. Samples were withdrawn at 0.5,1,2,3,4,6,8,10 and 12 h and the release was measured at the wavelength of 269 nm using UV-Vis spectrophotometry. Results:Gradient elution was used in the related substance test,and the main peak could be effectively separated from those of impurity A,impurity B and the other impurities. The contents of impurity A and impurity B in the samples were not more than 0.2%,and the total content of the impurities was not more than 0.5%. Equivalent elution was used in the content determination,and the sample content was (240.5±0.16) mg·g~(-1). The release curve profiles of the pellets showed similarity in five dissolution media and the cumulative release of the sample was over 80% within 12 hours. Conclusion: The determination method for the related substances is highly specific and sensitive,the method for the content determination and drug release both have good reproducibility and accuracy,which can be used for the quality control of pyridostigmine bromides sustained-release pellets.
引文
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3高建华,高秀蓉,许小红.溴吡斯的明的剂型研究进展[J].中国药房,2016,27(4):545~548
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5高建华,李泽民,高秀蓉,等.溴吡斯的明缓释微丸的制备及处方优化[J].中国医院药学杂志,2016,36(19):1670-1673
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8张明媛.三种化学药物中有关物质的分析方法研究[D].上海:第二军医大学硕士学位论文,2013
9武少馨,李丹.RP-HPLC法测定阿哌沙班片的含量及有关物质[J].中国药房,2015,26(6):828-831
10中国药典[S].2015年版.四部.121-124
2国家食品药品监督管理局.化学药物杂质研究的技术指导原则[EB/OL].(2007-08-23)[2018-12-06]http://www.cde.org.cn/zdyz.do?method=large Page&id=2060
3高建华,高秀蓉,许小红.溴吡斯的明的剂型研究进展[J].中国药房,2016,27(4):545~548
4 USP[S].USP40-NF-35.2010.2827
5高建华,李泽民,高秀蓉,等.溴吡斯的明缓释微丸的制备及处方优化[J].中国医院药学杂志,2016,36(19):1670-1673
6高建华.溴吡斯的明缓释微丸的制备及药动学评价[D].成都:成都医学院硕士学位论文,2016
7中国药典[S].2015年版.二部.1491-1492
8张明媛.三种化学药物中有关物质的分析方法研究[D].上海:第二军医大学硕士学位论文,2013
9武少馨,李丹.RP-HPLC法测定阿哌沙班片的含量及有关物质[J].中国药房,2015,26(6):828-831
10中国药典[S].2015年版.四部.121-124