葡萄糖酸钙口服溶液中5-羟甲基糠醛含量及来源分析

Analysis to Content and Source of 5-hydroxymethylfurfural(5-HMF)in Calcium Gluconate Oral Solution

目的:对葡萄糖酸钙口服溶液颜色与5-羟甲基糠醛(5-HMF)含量的相关性进行研究,分析制剂中5-HMF的来源并对药品进行风险控制。方法:采用HPLC方法,色谱柱:Aglea Venusil XBP C_(18)(250 mm×4.6 mm,5μm);流动相:水-乙腈(95∶5);流速1.0 mL·min^(-1);柱温30℃;检测波长284 nm;进样量10μL。结果:应用该方法测定166批次有糖型和42批次无糖型葡萄糖酸钙口服溶液,发现有糖型样品中,5-HMF含量在0μg·mL^(-1)至91μg·mL^(-1)之间,差异较大,其产生与制剂中辅料蔗糖的质量、溶解的温度、灭菌温度控制有关,且随着5-HMF含量的增加,样品溶液的颜色逐渐加深。结论:蔗糖作为葡萄糖酸钙口服溶液的辅料,在高温及弱酸条件下可降解生成5-HMF并影响产品颜色和质量,因此要严格控制辅料蔗糖的质量,加强生产工艺过程中配液和灭菌温度以及时间的控制,以减少5-HMF的生成,降低药品风险。

Objective:To study the correlation between the color of calcium gluconate oral solution and the content of 5-hydroxymethylfurfural(5-HMF),analyze the source of 5-HMF in the preparation and control the risk of drugs.Methods:HPLC method was used,and the column was Aglea Venusil XBP C_(18)(250 mm×4.6 mm,5μm),Mobile phase was water-acetonitrile(95∶5),The flow rate was 1.0 mL·min^(-1),Column temperature was 30℃,The detection wavelength was 284 nm,The injection volume was 10μL.Results:The method was applied to determine 166 batches of sugary calcium gluconate oral solution and 42 batches of sugar-free calcium gluconate oral solution.It was found that the content of 5-HMF in sugary samples was 0-91μg·mL^(-1).The diff erence was large,which was related to the quality of the auxiliary sucrose in the preparation,the dissolution temperature and the sterilization temperature control.With the increase of 5-HMF content,the color of the sample solution gradually deepened.Conclusion:As the auxiliary material of calcium gluconate oral solution,sucrose will degrade to form 5-HMF under high temperature and weak acid conditions and aff ect the color and quality of products.Therefore,the quality of sucrose as auxiliary material should be strictly controlled,and the liquid preparation,sterilization temperature and the time in the production process should be controlled so as to reduce the generation of 5-HMF and the risk of drugs.