GC法测定聚山梨酯65/85中乙二醇、二甘醇、三甘醇及环氧乙烷和二氧六环杂质的含量  

Determination of ethylene glycol,diethylene glycol,triethylene glycol,ethylene oxide and dioxane impurities in polysorbate 65/85 by GC

作　　者：王会娟 王珏[2] 王晓锋 孙会敏[2] 肖新月[2] 杨锐[2] 孙晶波[1] WANG Hui-juan;WANG Jue;WANG Xiao-feng;SUN Hui-min;XIAO Xin-yue;YANG Rui;SUN Jing-bo(Pharmaceutical College of Beihua University,Jilin 132013,China;National Institutes for Food and Drug Control,NMPA Key Laboratory for Quality Research and Evaluation of Pharmaceutical Excipients,Beijing 100050,China)

机构地区：[1]北华大学药学院,吉林132013 [2]中国食品药品检定研究院国家药品监督管理局药用辅料质量研究与评价重点实验室,北京100050

出　　处：《药物分析杂志》2022年第9期1634-1642,共9页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立新型药用辅料聚山梨酯65/85中乙二醇、二甘醇和三甘醇以及环氧乙烷和二氧六环杂质的检查方法。方法:乙二醇、二甘醇和三甘醇的检测为气相色谱直接进样法;环氧乙烷和二氧六环的检测为顶空气相色谱法。2种检查方法均为氢火焰离子化检测器(FID)。结果:乙二醇、二甘醇和三甘醇分别在5.10~101.92、5.06~101.28、5.00~100.04μg·mL^(-1)的浓度范围内线性关系良好(r=1.000;r=0.9999;r=0.9998);检测限分别为0.27、0.25、0.29μg·mL^(-1);定量限分别为0.55、0.50、1.15μg·mL^(-1);重复性RSD均<5%;回收率在91.3%~97.3%。环氧乙烷和二氧六环分别在1.00~10.00、0.50~40.00μg·mL^(-1)浓度范围内线性关系良好(r=0.9998;r=0.9999);检测限分别为0.15、0.32μg·mL^(-1);定量限分别为0.82和0.50μg·mL^(-1);重复性的RSD均<5.0%;回收率在96.6%~107.7%。19批聚山梨酯65/85样品中乙二醇、二甘醇以及三甘醇的含量结果分别在0~0.0006%、0~0.0009%、0.0009%~0.0032%;环氧乙烷和二氧六环含量结果分别在0~0.00025%、0~0.0126%。结论:本文建立的杂质检测方法灵敏度高,专属性和重复性良好,线性和回收率均符合2020年版《中华人民共和国药典》要求,适用于检测聚山梨酯65/85中的的乙二醇、二甘醇和三甘醇以及环氧乙烷和二氧六环杂质。Objective:To establish methods for the determination of ethylene glycol,diethylene glycol,triethylene glycol,ethylene oxide and dioxane innovel pharmaceutical excipient polysorbate 65/85.Methods:Ethyleneglycol,diethylene glycol and triethylene glycol were detected by gas chromatography.Ethylene oxide and dioxane were detected by headspace gas chromatography.Hydrogen flame ionization detector(FID)were used in both methods.Results:The linear relationships of ethylene glycol,diethylene glycol and triethylene glycol were good in the concentration ranges of 5.10-101.92μg·mL^(-1),5.06-101.28μg·mL^(-1),5.00-100.04μg·mL^(-1)(r=1.000;r=0.9999;r=0.9998).The detection limits were 0.27μg·mL^(-1),0.25μg·mL^(-1)and 0.29μg·mL^(-1).The limits of quantitation were 0.55μg·mL^(-1),0.50μg·mL^(-1)and 1.15μg·mL^(-1).The RSDs of repeatability were lower than 5%.The recoveries were in the range of 91.3%-97.3%.The linear relationships were good in the concentration ranges of 1.00-10.00μg·mL^(-1),0.50-40.00μg·mL^(-1)(r=0.9998;r=0.9998).The detection limits were 0.15μg·mL^(-1),0.32μg·mL^(-1).The limits of quantitation were 0.82,0.50μg·mL^(-1).The RSDs of repeatability were lower than 5%.The recoveries were in the range of 96.6%-107.7%.The contents of ethylene glycol,diethylene glycol and triethylene glycol in 19 batches of polysorbate 65/85 samples were 0-0.0006%,0-0.0009%and 0.0009%-0.0032%respectively.The contents of ethylene oxide and dioxane were 0-0.00025%and 0-0.0126%respectively.Conclusion:The impurities detection methods established in this paper have good sensitivity,specificity and repeatability.The linearity and recovery are in line with the requirements of Chinese Pharmacopoeia.It is suitable for the determination of ethylene glycol,diethylene glycol and triethylene glycol,ethylene oxide and dioxane impurities in polysorbate 65/85.

关 键 词：聚山梨酯 乙二醇 二甘醇 三甘醇 环氧乙烷 二氧六环 气相色谱法 

分 类 号：R917[医药卫生—药物分析学]