右旋糖酐40葡萄糖注射液中遗传毒性降解杂质含量测定及风险因素分析

Determination of Genotoxic Degradation Impurities in Dextran 40 Glucose Injection and Analysis of Risk Factors

关键词:  右旋糖酐40葡萄糖注射液|5-羟甲基糠醛|糠醛|遗传毒性|杂质

Key words:  dextran 40 glucose injection|5-hydroxymethyl furfural|furfural|genetic toxic|impurities

摘要:

目的 测定右旋糖酐40葡萄糖注射液中遗传毒性降解产物5-羟甲基糠醛和糠醛的含量并分析风险因素。方法 采用HPLC测定右旋糖酐40葡萄糖注射液及其原料药右旋糖酐40、葡萄糖中的5-羟甲基糠醛和糠醛含量，考察原料、工艺参数（温度、pH值）以及储存时间对杂质含量的影响。结果 5-羟甲基糠醛和糠醛在0.12~12.43 μg·mL^-1和0.03~8.60 μg·mL^-1内线性关系良好。右旋糖酐40葡萄糖注射液中相关杂质含量受工艺参数（温度、pH值）和存储时间影响，原料药基本不影响杂质含量。结论 应重点关注生产工艺中涉及原料药加热溶解温度和调节pH值的关键工艺参数，以提高制剂稳定性，同时应关注存储时间过长所引起的相关杂质增加。

Abstract:

OBJECTIVE To determine the content of 5-hydroxymethyl furfural and furfural, which are the genotoxic degradation products of dextran 40 glucose injection, and to analyze the risk factors. METHODS HPLC was used to determine the content of 5-hydroxymethyl furfural and furfural in dextran 40 glucose injection, and raw materials of dextran 40 and glucose. The effects of raw materials, process parameters(temperature, pH value), and storage time on the contents of degradation products were investigated. RESULTS The content of 5-hydroxymethyl furfural and furfural was linear in the range of 0.12-12.43 μg·mL^-1 and 0.03-8.60 μg·mL^-1. The content of degradation impurities in dextran 40 glucose injection was affected by process parameters(temperature, pH value) and storage time, raw materials didn't affect its content. CONCLUSION It is necessary to pay more attention to the key process parameters related to heating dissolution and adjusting pH value in the production process, so as to improve the stability of the dextran 40 glucose injection. At the same time, attention should be paid to the increase of related impurities caused by excessive storage time.