肝素钠注射液中的可见异物成因与定性方法研究

Cause and qualitative method study of visible particles in heparin sodium injection

目的:尝试运用先进仪器手段对肝素钠注射液中可见异物进行定性分析,进而对其可见异物的来源进行初步分析,并提出有的放矢的控制可见异物措施。方法:对收集到的肝素钠注射液样品,分别采用人工灯检法、扫描电镜-能谱分析(Scanning electron mictoscopy-X-ray energy dispersive analysis,SEM-EDX)和微流成像颗粒分析系统(Microfluidic imaging particle analysis system,MFI)三种方法进行可见异物检查和定性分析,同时考察不同放置条件对肝素钠注射液中可见异物生成的影响,汇总结果并予以分析。结果:目视和仪器方法在不同包装、不同生产工艺、不同批次产品中均可检出纤毛、玻璃、内源性物质等可见异物,但仪器方法在检出灵敏度和定性精准度方面优于目视。结论:应把先进的仪器手段运用到可见异物定性与成因研究中来,并从物料、包材、生产工艺、环境、人员等生产全流程对可见异物进行控制,减少可见异物的产生。

Objective:To develop new qualitative analysis methods of visible particles in heparin sodium injection by advanced analytical method,preliminary analyze the sources of visible particles,and measures to control the production of visible particles.Methods:The visible particles of heparin sodium injection samples were examined and qualitative analyzed by artificial lamp test,Scanning electron mictoscopy-X-ray energy dispersive analysis(SEM-EDX)and microfluidic imaging particle analysis system(MFI)respectively,and influences of different placement condition to the visible particles of heparin sodium injection samples.The results were summarized and analyzed.Meanwhile,the exogenous factors and endogenous factors on the causes of visible particles of heparin sodium injection were investigated.Results:Visible particles such as cilia,glass and endogenous substances were detected in the samples with different packages,different manufacture processes as well as different batches of samples by artificial lamp test and instrumental methods,and instrumental methods were superior in sensitivity and qualitative accuracy.Conclusion:The advanced instrumental methods should be used in the cause and qualitative method study of visible particles,and visible particles should be controlled from the whole process,including raw materials,packages,manufacture processes,environment and personnel,so as to reduce the production of visible particles.