基于遗传毒性谈5-羟甲基糠醛在含糖口服溶液剂中的风险控制研究  

Study on risk control of 5-hydroxymethyl furfural in sugar-containing oral solution drugs based on its genotoxicity

作　　者：伍良涌[1] 周远华[1] 赵雪梅[1] 李玮玲[1] 董顺玲[1] WU Liang-yong;ZHOU Yuan-hua;ZHAO Xue-mei(Guangzhou Institute for Drug Control,Guangzhou 510160,China)

机构地区：[1]广州市药品检验所,广州510160

出　　处：《中国处方药》2023年第9期36-39,共4页Journal of China Prescription Drug

基　　金：广州市市场监督管理局科技项目资助(2022kj31)。

摘　　要：目的根据5-羟甲基糠醛的遗传毒性评价,提出其在含糖口服溶液剂中控制的必要性。方法建立5-羟甲基糠醛通用的高效液相色谱检测方法,选取部分含糖口服溶液剂检测其中5-羟甲基糠醛的含量;根据药物临床用量计算5-羟甲基糠醛的暴露量,并按照遗传毒性杂质相关指导原则的要求对其标准限度进行评估。结果选取的含糖口服液体制剂中大部分检出5-羟甲基糠醛,且部分含量超出了拟定限度,存在安全隐患。结论5-羟甲基糠醛为2类遗传毒性杂质,建议含糖口服液体制剂的标准中应考虑建立5-羟甲基糠醛检查项,为生产企业改进工艺提供参考。Objective According to assess the genotoxicity of 5-hydroxymethyl furfural,to discuss the necessity of controlling 5-hydroxymethyl furfural in sugar-containing oral solution drugs.Methods A general HPLC method was established to determine the content of 5-hydroxymethyl furfural,and some sugar-containing oral solution drugs were selected to detect the content.The potential exposure of 5-hydroxymethyl furfural was calculated based on the dosages of drugs.Then the limit of 5-hydroxymethyl furfural was evaluated according to guidelines for genotoxic impurities.Results Most selected sugar containing oral solution drugs were detected 5-hydroxymethyl furfural,and some of them exceeded the proposed limits,that indicated too high to ensure the drugs’safety.Conclusion 5-hydroxymethyl furfural is a class 2 genotoxic impurity.It is suggested that consideration of the determination of 5-hydroxymethyl furfural in the quality standard of sugar containing oral solution drugs.The established analytical method can be used to provide reference for the quality control of sugar containing oral solution drugs and the improvement of production process.

关 键 词：高效液相色谱法 含糖口服液体剂 5-羟甲基糠醛 遗传毒性杂质 风险控制 

分 类 号：R927.2[医药卫生—药学]