注射用泮托拉唑钠的杂质含量及其杂质谱的比较

Comparison of Impurity Quality and Spectra in Pantoprazole Sodium for Injection

目的:建立注射用泮托拉唑钠杂质含量的检测方法,比较其国产品与原研品杂质谱。方法:采用液相色谱法进行注射用泮托拉唑钠杂质含量检查的方法学研究、定位及稳定性考察;采用迪马C18(4.6 mm×250 mm,5μm)色谱柱,流动相采用磷酸氢二钾溶液-乙腈行梯度洗脱,流速为1 m L/min,检测波长为290 nm和305 nm,柱温为40℃。结果:系统适应性试验示各杂质分离良好,能有效定位;供试品经强制破坏后各杂质峰与主峰均能达到完全分离,热破坏产生杂质-A和杂质-D(F),经碱、氧、光破坏后产生杂质-A和酸破坏后产生杂质-D/F和B;二者条件下均不产生杂质-C和杂质-E;改变柱温、流速、色谱柱品牌时,其方法耐用性较好;供试品溶液在6 h内其杂质含量RSD均小于2.0%,最低检测限均在0.01%以下,精密度RSD小于2.0%;杂质-A、杂质-B、杂质-C、杂质-D(F)、杂质-E的校正因子分别为1.04、0.98、0.33、1.15和1.10;留样稳定性经检测杂质-A和杂质-D(F)含量有所增长。结论:建立的有关物质检测方法操作较简便易行、耐用性好、专属性强和灵敏度高;实验结果表明杂质-A和杂质-D(F)为降解杂质,其余为工艺杂质;泮托拉唑钠国产品与原研品杂质种类一致,杂质数量相当,提示两者有关物质水平基本一致。

Objective：To establish the determination methods of impurity quality of pantoprazole sodium for injection and to compare the impurity spectra of its domestic and the original drug by HPLC. Methods：By HPLC validating the detection and stability studies. Diamonsil C18（250 mm×4.6 mm, 5 μm）column was adopted. A mixture of dipotassium hydrogen phosphate solution-acetonitrile was as the mobile phase, at the flow rate of 1.0 m L/min. The determination was carried out at wavelength 290 nm and 305 nm. The column temperature was set at 40 ℃. Results：The system had good suitability. After the test by forcing destructing, the system still could reach the baseline separation. Destroyed by heat, test solution could generate impurity A and D（F）, destroyed by alkali, oxidation and allochromatic could generate impurity A,destroyed by acid could generate impurity D（F） and B,and all destroyed factors could not generate impurity C and E. Changing the column temperature, flow rate and column, and all of the RSD was less than 2.0%, The test solution in 6 hours was stablic, and the RSD of the impurity content was less than 2.0%;The impurities＇ LOD were all less than 0.01%; The correction factors of the impurity A, B, C, D（F）. E with reference to pantoprazole were followed by1.04, 0.98, 0.33, 1.15 and 1.10;in the stability studies,impurity A and D（F） are increased. Conclusion：This method is relatively simple, specific of good durability and accuracy. The impurity A and D（F） were degradation impurities, the others are process impurities. By the comparison, the results show the domestic product and original product have good similarity in impurities quality.