克林霉素磷酸酯注射液热稳定性研究及其降解产物的LC-MS初步鉴定

Study on Thermal Stability of Clindamycin Phosphate Injection and Identification of Its Degradation Products by LC-MS

目的对不同厂家生产的克林霉素磷酸酯注射液的热稳定性进行了研究并对其主要降解产物进行LC-MS鉴定。方法在水浴条件下对样品进行热降解,分别在5,10min取样进行HPLC检测。采用欧洲药典(EP5.0)克林霉素磷酸酯HPLC色谱条件进行热稳定性研究。色谱柱为Thermo BDS HYPERSIL C18(4.6mm×150mm,5μm),流动相为13.6g·L-1磷酸二氢钾(磷酸调节pH值为2.5)-乙腈(80∶20);流速,1.0mL·min-1,检测波长,210nm。同时对其主要降解产物进行LC-MS鉴定。结果经过热降解实验,不同厂家样品中3个主要杂质的含量及杂质总量均增加,除克林霉素已知外,其他两个主要杂质采用LC-MS进行了鉴定。结论克林霉素磷酸酯注射液受热易降解不适于采用湿热灭菌法进行灭菌,并且不同厂家样品中所含主要杂质均相同,通过对杂质结构的鉴定,从而为克林霉素磷酸酯生产工艺的优化以及如何更好的减少杂质的生成提供了理论基础。

OBJECTIVE To investigate the thermal stability of clindamycin phosphate injection of different manufacturers and identify the degradation products by LC-MS. METHODS The samples were heated in water bath and sampled at 5,10 min. The mobile phase consisted of 13.6 g.L^-1 potassium dihydrogen phosphate （adjust the solution with phosphoric acid to pH 2.5）- acetonitrile（80 ： 20） at a flow rate of 1.0 mL.min^-1. The detection wavelength was 210 nm. The column was Thermo BDS HYPERSIL C18 （4.6 mm × 150 mm, 5 μ m） . The major degradation products was identified by LC-MS. RESULTS After the thermal degradation, the content of three major impurities and the sum content of impurities all increased in different samples. Except for Clindamycin, others were identified by LC-MS. CONCLUSION Clindamycin phosphate injection is unsuitable to moist heat sterilization because of its thermal instability, and the major impurities are same in three samples. After identification of the impurities, the results are important for optimizing the process and helpful to decrease the content of the impurities.