国产注射用阿奇霉素杂质谱及其与成盐工艺相关性的考察

目的: 考察国产不同成盐注射用阿奇霉素所含杂质谱情况,并对其工艺进行相关性评价。 方法: 以217批注射用阿奇霉素有关物质HPLC检验数据为基础,采用数理统计与化学计量学方法,对其杂质谱及与成盐工艺相关性进行考察,并通过加速实验验证考察结果。 结果: 所检样品中均检出阿奇霉素B(EP-B)和3'-去克拉定糖阿奇霉素(EP-J)杂质,且在不同厂家、不同成盐工艺产品中变化幅度较大,统计标准偏差(SD)分别达2.5和2.0;其他杂质还检出阿奇霉素-N-氧化物(EP-L)、氮红霉素(EP-A)。 结论: 目前国产注射用阿奇霉素中主要杂质为阿奇霉素-N-氧化物、3'-去克拉定糖阿奇霉素、氮红霉素和阿奇霉素B;氮红霉素和阿奇霉素B为工艺杂质,分别源于合成反应残留和起始原料红霉素中红霉素B残留;阿奇霉素-N-氧化物和3'-去克拉定糖阿奇霉素分别为阿奇霉素氧化和酸降解物,其中酸降解物为主要降解形式;不同厂家注射用阿奇霉素中所含杂质的种类、数目及水平均存在较大差异,且与其成盐工艺密切相关。

Objective: To investigate the impurity profile status of domestic azithromycin for injection by using different salifiable technologies,and evaluate the correlation of its crafts. Methods: Based on 217 batches of impurity testing datas of azithromycin for injection by HPLC,investigate the impurity profile and correlation of its salifiable technologies according to mathematical statistics and chemometrics methods,and validate the investigate results by using acceleration experiment. Results: Azithromycin B(EP-B) and 3'-decladinosyl azithromycin (EP-J) had been detected in all the samples,and there are large rangeability among the different factories and salifiable technological samples,the SD was 2.5 and 2.0;other impurities exist in samples included azithromycin-N-oxides(EP-L)and azithromycin A(EP-A)yet. Conclusion: The main imurities of domestic azithromycin for injection in now were azithromycin-N-oxides(EP-L),3'-decladinosyl azithromycin (EP-J),azithromycin A(EP-A)and azithromycin B(EP-B),azithromycin A and azithromycin B was craft impurities,derived from residues between synthetic reaction and erythromycin B in original material;azithromycin-N-oxides and 3'-decladinosylazithromycin were degradation products by oxidation and acidation,and acidation products was major degradative form.There are biggish distinction for species,amounts and levels of impurities of azithromycin for injection exsited in differ factories,it was closely correlation to their salifiable craft.