HPLC法测定缩宫素注射液中三氯叔丁醇的含量及其应用

HPLC Determination of Chlorobutanol in Oxytocin Injection and Applications

目的：针对缩宫素注射液现行标准中未对抑菌剂三氯叔丁醇进行控制的情况，建立缩宫素注射液中三氯叔丁醇的HPLC测定法，并对不同企业生产的401批缩宫素注射液样品进行测定。方法：采用Waters XBridge-C18色谱柱（4.6 mm ×250 mm，5μm），以0.1 mol· L^-1磷酸盐缓冲液作为流动相A，以水-乙腈（1∶1）作为流动相B，梯度洗脱，柱温40℃，流量为1.0 mL·min^-1，检测波长为220 nm。结果：在选定的色谱条件下，三氯叔丁醇主峰和缩宫素主峰、杂质峰分离良好；三氯叔丁醇在浓度15.62～2000μg· mL^-1范围内峰面积与浓度呈良好线性关系，r＝1.0000；平均回收率98.6％（n＝9）。401批缩宫素注射液中，三氯叔丁醇含量为0～1.78 mg· mL^-1，不同企业间差异显著，且与处方量有一定差异。结论：该法专属性强，灵敏、准确，可作为缩宫素注射液中三氯叔丁醇的质量控制方法。市售制剂中的三氯叔丁醇含量在企业之间、企业内批间差异较大，且与处方标示量对应性较差。因此，有必要在缩宫素注射液中，增加三氯叔丁醇含量的检测项，以监控该品种中抑菌剂含量，促进企业稳定生产工艺，确保产品质量稳定、安全、有效。

Objective：To develop a gradient liquid chromatographic method for the determination of chlorobutanol in Oxytocin Injection and analyze 401 batches of Oxytocin Injection samples.Methods： A Waters XBridge-C18 column （4.6 mm ×250 mm, 5 μm） was used for the gradient elution.The mobile phases consisted of 0.1 mol· L^-1 phosphate buffer as A and water-acetonitrile （1∶1） as B, the flow rate was 1.0 mL· min^-1 ,UV detection was performed at 220 nm and the column temperature was set to 40℃.Results：Chlo-robutanol was well separated from oxytocin and its related substances by the established method.The calibration curve was linear be-tween peak area and oxytocin concentration at the range of 15.62-2000μg· mL^-1 with r=1.0000, the average recovery （ n=9） was 98.6%.In 401 batchs of Oxytocin Injection samples, the contents of chlorobutanol were 0-1.78 mg· mL^-1.Conclusion：The meth-od is proved to be specific, sensitive and accurately and could be used to control the quality of Oxytocin Injection.Furthermore the re-search results showed the contents of chlorobutanol had significant differences between manufacturers and batches, prescription and the actual content, it is necessary to improve the quality standards of Oxytocin Injection to control the content of chlorobutanol, ensuring the stability, safety and effectivity of the products.