HPLC法测定艾司奥美拉唑钠中3个潜在基因毒性杂质的研究及控制
Determination of three genotoxic impurities in esomeprazole sodium by HPLC
曹盼 1吴会斌 2陈焱 2赵龙山1
作者信息
- 1. 沈阳药科大学,沈阳 110016
- 2. 辽宁海思科制药有限公司,葫芦岛 125107
- 折叠
摘要
目的:建立HPLC法测定艾司奥美拉唑钠中潜在基因毒性杂质E、杂质Ⅰ、2-氯甲基-3,5二甲基-4-甲氧基吡啶.方法:杂质E色谱条件:YMC-Triart C18色谱柱(250 mm×4.6 mm,5 μm),流动相A为0.05 mol·L-1磷酸二氢钾缓冲液,流动相B为乙腈,梯度洗脱,流速为1.0 mL·min-1,检测波长为302 nm,柱温为 30 ℃;杂质 Ⅰ 色谱条件:Agilent Microspher C18 色谱柱(100 mm ×4.6 mm,3 μm),流动相A为水-磷酸盐缓冲液(pH 7.6)-乙腈(80∶10∶10),流动相B为乙腈-磷酸盐缓冲液(pH 7.6)-水(80∶1∶19),梯度洗脱,流速为1.0 mL·min-1,检测波长为302 nm,柱温为30℃;2-氯甲基-3,5二甲基-4-甲氧基吡啶色谱条件:GL Inertsil ODS-3色谱柱(250 mm × 4.6 mm,5 μm),流动相A为0.01 mol·L-1磷酸氢二钠溶液(pH 6.5),流动相B为乙腈,流速为1.0 mL·min-1,检测波长为265 nm,柱温为30℃.结果:杂质E、杂质Ⅰ、2-氯甲基-3,5二甲基-4-甲氧基吡啶的线性范围分别为 0.025 1～0.200 7、0.020 2～0.302 7、0.126 6～2.110 0 μg·mL-1,定量限分别为 0.50、0.40、2.53 ng,检测限分别为0.15、0.12、0.84 ng.平均回收率都在96％～104％,RSD均＜2％.样品中均未检出潜在毒性杂质.结论:该方法检测杂质的重现性好,精密度高,准确度高,线性良好,分析方法简便高效.
Abstract
Objective:To establish an HPLC method for the determination of potentially genotoxic impurity E,impurity I,and 2-chloromethyl-4-methoxy-3,5-dimethlpyridine in esomeprazole sodium.Methods:The chromatographic conditions were as follows:impurity E,YMC-Triart C18 column(250 mm ×4.6 mm,5 μm),mobile phase A 0.05 mol·L-1 monopotassium phosphate buffer,mobile phase B was acetonitrile,the gradient e-lution program was used at the flow rate of 1.0 mL·min1,the detection wavelength was 302 nm and the column temperature was 30 ℃.Impurities I,Agilent Microspher C18 column(100 mm×4.6 mm,3 μm),mobile phase A was water-phosphate buffer(pH 7.6)-acetonitrile(80∶10∶10),mobile phase B was acetonitrile-phosphate buffer(pH 7.6)-water(80∶1∶19),the flow rate was 1.0 mL·min-1,the detection wavelength was 302 nm and the column temperature was 30 ℃.2-chloromethyl-4-methoxy-3,5-dimethlpyridine,GL Inertsil ODS-3 column(250 mm ×4.6 mm,5 μm),mobile phase A was 0.01 mol·L-1 disodium phosphate solution(pH 6.5),mobile phase B was acetonitrile,the flow rate was 1.0 mL·min-1,the detection wavelength was 265 nm and the column temperature was 30 ℃.Results:The linear ranges of impurity E,impurity I and 2-chloromethyl-4-methoxy-3,5-dimethlpyridine were 0.025 1-0.200 7,0.020 2-0.302 7,0.126 6-2.110 0 μg·mL-1.The LOQ of impurity E,impurity I,2-chloromethyl-4-methoxy-3,5-dimethlpyridine were 0.50,0.40,2.53 ng,and the LOD were 0.15,0.12,0.84 ng.The average recovery rate ranged from 96％to 104％,and the RSD was less than 2％.No potential toxic impurities were detected in the samples.Conclusion:The method has the advantages of good repeatability,high precision,high accuracy and good lineari-ty,and the analysis method are simple and efficient.
关键词
艾司奥美拉唑/基因毒性杂质/高效液相色谱法/杂质E/杂质Ⅰ/2-氯甲基-3,5二甲基-4-甲氧基吡啶Key words
esomeprazole/genotoxic impurities/high performance liquid chromatography/impurity E/impurity I/2-chloromethyl-4-methoxy-3,5-dimethlpyridine引用本文复制引用
出版年
2024
NETL
NSTL
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