摘要
目的:建立注射用阿奇霉素中杂质的液相检查方法,通过稳定性考察结合药审中心的要求,确定杂质的控制限度。方法:采用高效液相色谱法(HPLC)进行杂质检查的方法学研究及稳定性考察;采用Waters XTerra MS C18(5μm,250 mm×4.6 mm)色谱柱,流动相为磷酸氢二钠溶液-甲醇-乙腈进行梯度洗脱,流速为1 m L/min,检测波长为210 nm,柱温为55℃。结果:系统适应性试验各杂质分离良好,符合系统适用性要求;供试品经强制破坏后各杂质峰与主峰均能达到基线分离;杂质-L、杂质-J、杂质-N、杂质-B校正因子分别为2.3,1.0,0.7和1.0;改变柱温、流速、流动相p H值时,各杂质含量和总杂质含量均小于2.0%;供试品溶液在6 h内较稳定,杂质含量RSD均小于2.0%。结论:建立的有关物质检测方法简便易行、耐用性好,专属性强,灵敏;杂质检查采用校正因子进行定量控制,检测结果准确度高,且解决了杂质单体采购难题;本法适用于注射用阿奇霉素的杂质定量研究和控制。
Objective： To establish a HPLC method for the research and control of impurities in azithromycin for injection, through the stability studies and combined with the CDE＇s requirements, the control limits of impurities were determined. Methods：Using HPLC method to conduct the detection and stability studies. Waters XTerra MS C18（5 μm, 250 mm × 4.6 mm）column was adopted. The mobile phase consisted of a mixture of sodium dihydrogen phosphate- methanol-acetonitrile; the flow rate was 1.0 mL/min and the UV detection was carried out at wavelength 210 nm.The column temperature was set at 55 ℃. Results： The system has a good suitability. After the test by forcing destruction, the system still can reach the baseline separation. The correction factors of the Impurity L, J, N and B with reference to azithromycin were followed by 2.3,1.0,0.7 and 1.0. After Changing the colunan temperature, flow rate and mobile＇s pH, all of the RSD in single and total impurity contents less than 2.0%, The test solution in 6 hours is stable, and the RSD of the impurity content was less than 2.0%. Conclusion ： This method is selective, specific well durable and accurate. Using the correction factors to control the impurities, the difficulty to obtain the impurities could be solved.
出处
《抗感染药学》
2015年第2期174-178,共5页
Anti-infection Pharmacy
