中药注射剂不良反应早期预警方法的研究(Ⅰ)——安全相关物质5-羟甲基糠醛的研究  

Research on methods of early warning detection of adverse drug reactions in Chinese medicine injection(Ⅰ):Safety-related substances 5-HMF

作　　者：闫琰[1,2] 鄢丹 张萍[1] 张少锋 任永申 冯雪 肖小河[1] 

机构地区：[1]解放军第三〇二医院全军中药研究所,北京100039 [2]军事医学科学院毒物药物研究所,北京100850

出　　处：《中华中医药杂志》2010年第12期2268-2270,共3页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金资助项目(No.30701109);国家"重大新药创制"科技重大专项资助项目(No.2009ZX09502-003;No.2009ZX09502-022)~~

摘　　要：目的:考察安全相关物质5-羟甲基糠醛(5-HMF)在中药注射剂及其溶媒中的动态稳定性,作为中药注射剂不良反应早期预警方法的研究的组成部分,为中药注射剂安全性评价提供参考。方法:以注射用益气复脉(YQFM)为模式药,采用超高效液相色谱(UHPLC)动态监测法考察5-HMF在灭菌注射用水、5%葡萄糖注射液及含药溶媒中稳定性,并用傅立叶变换红外光谱(FTIR)予以佐证。结果:实验发现5-HMF在上述溶媒中均发生一定程度的降解,5-HMF在YQFM中0-90min的降解速率约为其他溶媒的5倍,静置210min后,各溶媒中5-HMF含量趋于稳定。5-HMF的UHPLC图谱存在裂解现象,并得到FTIR佐证,提示有新物质生成。结论:5-HMF在所选溶媒中不稳定,降解产物可能引发不良反应;建议应将5-HMF及其降解产物的动态监测作为中药注射剂安全性评价内容之一,以最大限度的减少不良反应的发生。Objective：To study security-related material 5-hydroxymethyl furfural（5-HMF）dynamic stability in the solvents and traditional Chinese medicine injection,as a part of early monitoring methods about Chinese medicine injection,to provide reference for the safety evaluation of traditional Chinese medicine injection.Method：The Yiqifumai injection（YQFM）as a model drug,using ultra-high performance liquid chromatography（UHPLC）dynamic monitoring the 5-HMF stability in sterile water for injection,5%glucose injection and drug-containing solvents was evidenced by Fourier transform infrared spectroscopy（FTIR）.Results：The experiments show tha when the 5-HMF degraded in the solvents in a certain degree,the degradation rate of 5-HMF in YQFM is about 5 times than the other solvents in 0-90min,5-HMF in the solvents after 210min,5-HMF＇s UHPLC chromatogram cracking and the FTIR evidenced the sample contained new substances.Conclusion：The 5-HMF is instability in the selected solvents and the degradation products may cause adverse reactions.The suggestion is the 5-HMF and its degradation products should be dynamic monitoring as a part of safety evaluation of TCM injections to reduce the incidence of adverse reactions.

关 键 词：5-羟甲基糠醛 溶媒 注射用益气复脉 稳定性 动态监测 安全相关物质 

分 类 号：R286[医药卫生—中药学]