目的 建立阿奇霉素颗粒中基因毒性杂质对甲苯磺酸乙酯的高效液相色谱（HPLC）测定方法。方法 采用Waters XBridge C₁₈（250 mm×4.6 mm，5 μm）色谱柱，以磷酸盐缓冲液（2.2 g·L^-1无水磷酸氢二钾溶液，用稀磷酸调节pH值至8.9）为流动相A；甲醇-乙腈（25∶75）为流动相B，进行梯度洗脱，体积流量为1.0 mL·min^-1，检测波长为225 nm，柱温为60℃，进样量为50 μL。进行专属性、线性关系、定量限和检测限、精密度、重复性、回收率、稳定性、耐用性试验。结果 空白溶剂、空白辅料、混合溶液中邻近对甲苯磺酸乙酯的杂质L均不干扰对甲苯磺酸乙酯检测；对甲苯磺酸乙酯质量浓度在0.05～0.20 μg·mL^-1（R²＝0.999 9）与峰面积呈良好线性关系；检测限为0.016 7 μg·mL^-1，定量限为0.050 0 μg·mL^-1；平均回收率为95.76%～96.48%，RSD为0.42%～1.53%；精密度、重复性、稳定性、耐用性均符合要求。3批样品中均未检出对甲苯磺酸乙酯。结论 建立的方法专属性强、灵敏度高、特异性强、准确度高，可用于阿奇霉素颗粒中基因毒性杂质对甲苯磺酸乙酯的限度控制与检测。

Objective To establish a high performance liquid chromatography (HPLC) method for the determination of genotoxic impurity ethyl p-toluenesulfonate in azithromycin granules. Methods The separation was performed on Waters XBridge C₁₈ column (250 mm×4.6 mm, 5 μm) at a flow rate of 1.0 mL·min^-1. The mobile phase A was phosphate buffer (2.2 g·L^-1 anhydrous dipotassium hydrogen phosphate solution, adjusted to pH 8.9 with dilute phosphoric acid), and mobile phase B consisted of methanol-acetonitrile (25:75) and gradient elution was performed. The detection wavelength was set at 225 nm, the column temperature was 60℃, and the injection volume was 50 μL. Specificity, linearity, limit of quantitation and detection, precision, repeatability, recovery, stability and durability tests are carried out. Results Blank solvent, blank excipient and impurity L nearest to ethyl p-toluenesulfonic acid in mixed solution do not interfere with ethyl p-toluenesulfonic acid detection. Good linear relationships between the concentration and the peak area of ethyl p-toluenesulfonate in the range of 0.05-0.20 μg·mL^-1(R²=0.999 9) was achieved. The limit of detection was 0.016 7 μg·mL^-1, and the limit of quantitation was 0.050 0 μg·mL^-1. The average recoveries were 95.76%-96.48%, RSD were 0.42%-1.53%. Precision, repeatability, stability and durability all meet the requirements. No genotoxic impurities ethyl p-toluenesulfonate was detected in three batches of samples. Conclusion This method has strong specificity, high sensitivity, high specificity and high accuracy, and can be used for the limit control and detection of ethyl p-toluenesulfonate, a genotoxic impurity in azithromycin granules.

R917