盐酸洛美沙星滴耳液中洛美沙星与辅料反应杂质研究

徐森敖; 周玉平; 周霞; 曾红霞; 伍义行

doi:10.13748/j.cnki.issn1007-7693.20252410

盐酸洛美沙星滴耳液中洛美沙星与辅料反应杂质研究

Study on the Reaction Impurity Between Lomefloxacin and Excipients in Lomefloxacin Hydrochloride Ear Drops

摘要

摘要:
目的对盐酸洛美沙星滴耳液中未知杂质进行结构鉴定、分析其产生原因，并建立新方法进行质量控制。
方法通过液相色谱-离子阱-飞行时间高分辨质谱联用技术(LC/IT-TOF-MS)分离鉴定未知杂质的结构，采用稳定性试验研究6个厂家不同处方工艺的产品，分析杂质产生机制，并对杂质分析方法进行验证。
结果确证该杂质为在温度较高的条件下，处方中的辅料甘油与洛美沙星哌嗪环上的碳氮键脱水缩合生成；新建立的HPLC分析方法专属性强，精密度、准确性、线性和耐用性均良好。
结论本研究对制剂研究中部分未知杂质的控制有一定的指导意义，提示部分企业应关注原料药与辅料相容性问题。

Abstract:
OBJECTIVE To identify the structure of unknown impurities in lomefloxacin hydrochloride ear drops, analyze their formation cause, and establish a novel method for quality control.
METHODS The structure of unknown impurity was identified using liquid chromatography-ion trap-time-of-flight high-resolution mass spectrometry(LC/IT-TOF-MS). Stability studies were conducted on products from six manufacturers with different formulations and processes to investigate the impurity formation mechanism. The impurity analytical method was validated.
RESULTS The impurity was confirmed to result from the dehydration and condensation reaction between glycerol(an excipient in the formulation) and the C-N bond on the piperazine ring of lomefloxacin under high temperature condition. The newly developed HPLC analytical method demonstrated strong specificity, as well as satisfactory precision, accuracy, linearity, and robustness.
CONCLUSION This study provides guidance for controlling certain unknown impurity in pharmaceutical formulations and highlights the need for domestic manufacturers to address compatibility issues between active pharmaceutical ingredients(APIs) and excipients.

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