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、5.00~100.04 μg·mL-1的浓度范围内线性关系良好(r乙二醇=1.000;r二甘醇=0.999 9;r三甘醇=0.999 8);检测限分别为0.27、0.25、0.29 μg·mL-1;定量限分别为0.55、0.50、1.15 μg·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、0.50~40.00 μg·mL-1浓度范围内线性关系良好(r环氧乙烷=0.999 8;r二氧六环=0.999 9);检测限分别为0.15、0.32 μg·mL-1;定量限分别为0.82和0.50 μg·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0~0.000 6%、 0~0.000 9%、0.000 9%~0.003 2%;环氧乙烷和二氧六环含量结果分别在0~0.000 25%、0~0.012 6%。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: Ethylene glycol, 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 5.10-101.92 μg·mL-1,5.06-101.28 μg·mL-1,5.00-100.04 μg·mL-1(rglycol=1.000; rdiethylene glycol=0.999 9; r triethylene glycol=0.999 8). The detection limits were 0.27 μg·mL-1,0.25 μg·mL-1 and 0.29 μg·mL-1.The limits of quantitation were 0.55 μg·mL-1,0.50 μg·mL-1 and 1.15 μg·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 1.00-10.00 μg·mL-1, 0.50-40.00 μg·mL-1 (rethylene oxide=0.999 8; rdioxane=0.999 8).The detection limits were 0.15 μg·mL-1, 0.32 μg·mL-1.The limits of quantitation were 0.82, 0.50 μg·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 0-0.000 6%, 0-0.000 9% and 0.000 9%-0.003 2% respectively. The contents of ethylene oxide and dioxane were 0-0.000 25% and 0-0.012 6% 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.
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