基于化学特征图谱-生物热活性图谱关联检测的注射用双黄连冻干粉针质量控制方法的初步研究  

Quality control of Shuanghuanglian freeze-dried powder for injection based on its HPLC-ELSD fingerprints and biological profiles

作　　者：张雅铭[1,2] 鄢丹[2] 张萍[2] 任永申[2] 张少峰[2] 冯雪[2] 肖小河[2] 

机构地区：[1]军事医学科学院毒物药物研究所,北京100850 [2]中国人民解放军第302医院全军中药研究所,北京100039

出　　处：《药学学报》2010年第1期93-97,共5页Acta Pharmaceutica Sinica

基　　金：国家"重大新药创制"科技重大专项资助项目(2009ZX09502-003;2009ZX09502-022);国家自然科学基金资助项目(30701109)

摘　　要：为了建立包括生物热活性检测在内的中药注射剂质量控制方法,本文以注射用双黄连冻干粉针为模式药,建立HPLC-ELSD特征图谱,进行相似度评价;采用微量量热法,建立生物热活性图谱,并提取相关生物热动力学参数(达峰时间Tm2,Tj和抑制率I%),以相关系数法进行相似度评价。结果表明,HPLC-ELSD特征图谱不易区分不同贮藏条件下样品之间的微小差异,特别是对生物污染样品基本无法辨识;生物热活性图谱可以区别高温处理样品及污染变质样品,并可以全面反映模型生物的热生物学信息,提供了专属性较强的二维信息,可作为化学特征图谱的有益补充。本文从质量均一性出发,通过HPLC-ELSD特征图谱和生物热活性图谱关联检测对注射用双黄连冻干粉针进行质量控制,为实现对中药注射剂质量变化的早期快速筛查,预警其不良反应提供了技术参考。This paper is aimed to provide the methods of quality control and bioassay of traditional Chinese medicine injections including bioassay method. Shuanghuanglian freeze-dried powder for injection （SFPI） was chosen as study object. HPLC-ELSD fingerprints of SFPI had been established and the samples were differentiated by similarity calculation. Meanwhile, biological profiles of SFPI on Escherichia coli had been established by microcalorimetry. The similarity values were calculated using the correlation coefficient, based on quantitative thermo-kinetic parameters （ Tm 2, Tj, I%）. The results indicated that HPLC-ELSD fingerprints, which showed content changes of chemical components, could not monitor minimal variation of different samples, especially that of biological pollutants, while biological profiles could sensitively detect antibiotic activity alterations of the samples, which were kept under specific conditions. In conclusion, characterized by two-dimension, microcalorimetry could supply thermograms as biological profiles characterized to describe the bioactivity of drugs. This study could clearly demonstrate that the correlative detection was proposed as an efficient strategy for quality control of SFPI, based on HPLC-ELSD fingerprints and biological profiles, which could detect quality fluctuation of samples early and quickly and predict the potential adverse drug events （ADE）for ensuring clinical safety.

关 键 词：注射用双黄连冻干粉针 HPLC-ELSD 生物热活性图谱 质量控制 均一性 

分 类 号：R917[医药卫生—药物分析学]