目的 建立乌司他丁中O-糖胺聚糖的鉴定与评价方法,为产品的质量一致性评价奠定基础。方法 利用化学降解与盐析法,将O-糖胺聚糖从乌司他丁糖蛋白中释放及沉淀分离,通过液相-三重四级轨道阱-高分辨质谱(UHPLC-Orbitrap-HRMS)技术,对O-糖胺聚糖进行质谱数据的采集与分析。结果 通过对3批乌司他丁溶液以及4批乌司他丁注射液中O-糖胺聚糖精确相对分子质量以及各分子离子峰响应强度比例进行解析与计算,证明企业A生产的乌司他丁产品与原研制剂中的O-糖胺聚糖的主要糖型基本一致。结论 本研究所建立的乌司他丁中O-糖胺聚糖的表征与评价方法准确、可靠、适用范围广,不仅能够实现对于乌司他丁产品中的O-糖修饰的质量评价,也能够对其他糖蛋白类药物的O-糖修饰表征与分析起到示范性作用。
Abstract
OBJECTIVE To establish a method for characterization and evaluation of the O-glycosaminoglycan in ulinastatin. METHODS The research released and separated the O-glycosaminoglycan through the chemical degrading and salt deposition, then acquired the mass data of the O-glycosaminoglycan via the UHPLC-Orbitrap-HRMS. RESULTS The result showed that the products derived from different companies are consistent in their O-glycosaminoglycan by the analysis and calculation of the molecular weight and molecular ion peaks. CONCLUSION The method for characterization of the O-glycosaminoglycan in ulinastatin in this research is precise and reliable which could not only realize to evaluate the quality of ulinastatin, but also could apply in other extracted glycoprotein drugs.
关键词
O-糖胺聚糖 /
乌司他丁 /
高分辨质谱 /
质量一致性评价
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Key words
O-glycosaminoglycan /
ulinastatin /
HRMS /
quality consistency evaluation
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中图分类号：
R284
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脚注
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基金
北京市自然科学基金项目资助(7194337)
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