HPLC-ECD法测定阿奇霉素缓释干混悬剂的有关物质

Determination of the Related Substances in Azithromycin Extended Release for Oral Suspension by HPLC-ECD

建立了高效液相色谱法-电化学检测(HPLC-ECD)法测定阿奇霉素(1)缓释干混悬剂的有关物质。采用ZirChrom-PBD色谱柱,流动相为磷酸二氢钾溶液∶乙腈(213∶87),等度洗脱,流速为0.6 ml/min,柱温为30℃,进样量为50μl。结果显示,1与各已知杂质[阿奇霉素N-氧化物(2)、阿奇霉素德糖胺(3)、N-去甲基阿奇霉素(4)、阿奇霉素有关物质F(5)、氮杂红霉素A(6)和阿奇霉素有关物质H(7)]及强制破坏产生的降解产物均分离良好;1~7在相应线性范围内线性关系良好(r≥0.9960)。1~7的平均回收率分别为96.0%、88.5%、98.1%、97.7%、100.0%、95.1%和98.6%,RSD(n=9)分别为1.86%、3.20%、1.25%、2.62%、4.06%、1.05%和2.95%;精密度试验RSD(n=6)分别为4.23%、2.65%、2.70%、4.57%、4.45%、0.96%和3.91%,均符合测定要求。本研究建立的方法灵敏度高、专属性强,可用于1缓释干混悬剂有关物质的检测。

A high performance liquid chromatography-electrochemical detection(HPLC-ECD)method was established for determination of the related substances in azithromycin(1)extended release for oral suspension.The ZirChrom-PBD column was used,with potassium dihydrogen phosphate solution and acetonitrile(213∶87)as mobile phase(isocratic elution).The flow rate was 0.6 ml/min,the column temperature was 30℃,and the injection volume was 50μl.The results showed that 1 and the known impurities[azithromycin N-oxide(2),azithromycin dexsamine(3),N-desmethyl azithromycin(4),azithromycin related substance F(5),azaerythromycin A(6)and azithromycin related substance H(7)],as well as the degradation products produced by the stress tests,were all separated well.And the calibration curves were linear for compounds 1-7 in the corresponding ranges(r≥0.9960).The average recoveries of1-7 were respectively 96.0%,88.5%,98.1%,97.7%,100.0%,95.1%and 98.6%with the RSDs(n=9)of 1.86%,3.20%,1.25%,2.62%,4.06%,1.05%and 2.95%.The precision test RSDs(n=6)were 4.23%,2.65%,2.70%,4.57%,4.45%,0.96%and 3.91%,respectively.All of the data met the requirements of quantitative analysis.This method has high sensitivity and strong specificity,which can be used for the detection of related substances in 1 extended release for oral suspension.