肌苷注射剂杂质分析及处方工艺合理性探讨  

Impurity analysis of inosine injection and discussion on rationality of their formulations and processes

作　　者：阚微娜 王棘 杨宏伟 KAN Weina;WANG Ji;YANG Hongwei(Liaoning Institute for Drug Control,Shenyang 110036,China)

机构地区：[1]辽宁省药品检验检测院,沈阳110036

出　　处：《中国药品标准》2021年第5期413-417,共5页Drug Standards of China

基　　金：国家标准提高课题:课题编号:2018H058,2020H021等。

摘　　要：目的:建立肌苷注射剂杂质分析方法,评价处方工艺合理性。方法:采用高效液相色谱法,色谱柱为Agilent TC C_(18)-2(4.6 mm×250 mm,5μm),以甲醇-水(5∶95)为流动相,流速1.0 mL·min^(-1),柱温30℃;检测波长248 nm(5-羟甲基糠醛检测波长280 nm),进样量10μL;通过破坏实验、原料及四种肌苷注射剂共计18批次样品杂质的测定,分析肌苷原料和注射剂杂质的来源。结果:肌苷原料的工艺杂质为鸟苷、次黄嘌呤和腺苷,注射剂中主要降解杂质为次黄嘌呤,5-羟甲基糠醛为肌苷葡萄糖注射液中葡萄糖的降解产物;肌苷及各已知杂质之间分离度良好。结论:现行质量标准应增加已知杂质及其他单个杂质的控制,由于处方及工艺合理性存在问题,肌苷注射液与肌苷葡萄糖注射液两种剂型安全性存在一定风险。Objective:To establish an impurity analysis method for inosine injections and evaluate the rationality of formulations and processes.Methods:HPLC separation was carried out in an Agilent TC C_(18)-2 column(4.6 mm×250 mm,5μm)under the isocratic elution of methanol-water(5∶95).The flow rate was 1.0 mL·min^(-1)and the column temperature was 30℃.The detection wavelength was 248nm(280nm for 5-hydroxymethyl furfural)and the injection volume was 10μL.The sources of impurities of drug substance of Inosine and Inosine Injections were analyzed by the degradation test and the impurities determination of 18 batches of drug substance of inosine and four kinds of Inosine Injections.Results:Guanosine,hypoxanthine and adenosine were identified as the process impurities of Inosine.Hypoxanthine was the main degradation impurity in Inosine Injections,5-hydroxymethyl furfural was the degradation product of glucose in Inosine Glucose Injection.The resolutions between inosine and the known impurities peaks were good.Conclusion:The known impurities and other individual impurity should be controlled in the specifications.Due to the problems of rationality of formulations and processes,Inosine Injection and Inosine Glucose Injection have certain safety risks.

关 键 词：肌苷注射液 注射用肌苷 肌苷氯化钠注射液 肌苷葡萄糖注射液 杂质 剂型合理性 

分 类 号：R921.2[医药卫生—药学]