高效分子排阻色谱法测定涉药品不良反应注射用曲克芦丁中多糖和蛋白类大分子物质  

Determination of Polysaccharide and Protein Macromolecular Substances in Troxerutin for Injection Related to Adverse Drug Reactions by HPSEC

作　　者：张琪 于德志 高倩 李会轻 杨钊 ZHANG Qi;YU Dezhi;GAO Qian;LI Huiqing;YANG Zhao(Qingdao Institute of Food and Drug Control·NMPA Key Laboratory for Quality Research and Evaluation of Traditional Marine Chinese Medicine,Qingdao,Shandong,China 266071)

机构地区：[1]山东省青岛市食品药品检验研究院·国家药品监督管理局海洋中药质量研究与评价重点实验室,山东青岛266071

出　　处：《中国药业》2023年第13期86-90,共5页China Pharmaceuticals

摘　　要：目的采用高效分子排阻色谱(HPSEC)法测定涉药品不良反应(ADR)注射用曲克芦丁中多糖和蛋白类大分子的含量。方法检测器为示差折光检测器,色谱柱为TSKgel G4000PWXL凝胶柱(300 mm×7.8 mm,10μm),流动相为纯化水,流速为0.5 mL/min,柱温为35℃,以不同相对分子质量右旋糖酐标准品为对照,对注射用曲克芦丁中多糖类大分子物质进行筛查;检测器为紫外检测器,色谱柱为TSKgel G2000SWXL凝胶柱(300 mm×7.8 mm,10μm),流动相为乙腈-水-三氟乙酸(45∶55∶0.05,V/V/V),流速为0.8 mL/min,检测波长为214 nm,以生长抑素、胸腺肽α1、人胰岛素、核糖核酸酶A为对照,对注射用曲克芦丁中蛋白类大分子物质进行筛查。结果涉ADR批次及正常批次注射用曲克芦丁中多糖类大分子物质的数据无明显差异;涉ADR批次中蛋白类大分子物质的含量高达正常批次的3倍,且制剂对应厂家的曲克芦丁原料药中蛋白类大分子物质的含量远高于同测第三方厂家曲克芦丁原料药的20倍。结论该研究中注射用曲克芦丁发生ADR的原因为产品中蛋白类大分子物质的含量偏高。Objective To determine the content of polysaccharides and protein macromolecules in the batches of Troxerutin for Injection related to adverse drug reactions(ADR)by the high-performance size exclusion chromatography(HPSEC)method.Methods Differential refractive index detector(RID)was adopted,the chromatographic column was TSKgel G4000PWXL gel column(300 mm×7.8 mm,10μm),the mobile phase was purified water,the flow rate was 0.5 mL/min,the column temperature was 35℃,and the polysaccharide macromolecules in Troxerutin for Injection were screened with the series of dextran standards with different molecular weight as the control.Ultraviolet(UV)detector was adopted,the chromatographic column was TSKgel G2000SWXL gel column(300 mm×7.8 mm,10μm),the mobile phase was acetonitrile-water-trifluoroacetic acid(45∶55∶0.05,V/V/V),the flow rate was 0.8 mL/min,the detection wavelength was 214 nm,and the protein macromolecules in Troxerutin for Injection were screened with the somatostatin,thymosinα1,human insulin and ribonuclease A as the control.Results There was no significant difference in the data of polysaccharide macromolecular substances between ADR-related batches and normal batches of Troxerutin for Injection.However,the content of protein macromolecular substances in ADR-related batches reached about three times that in the normal batches,and the content of protein macromolecular substances of the troxerutin raw material from the corresponding manufacturer of the preparation was more than 20 times that from the third-party manufacturer.Conclusion The cause of ADR of Troxerutin for Injection is the uncontrolled high content of protein macromolecular substances in the product.

关 键 词：高效分子排阻色谱法 注射用曲克芦丁 药品不良反应 大分子物质 

分 类 号：R927.2[医药卫生—药学] R973.2