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.
WANG Hui-juan, WANG Jue, WANG Xiao-feng, SUN Hui-min, XIAO Xin-yue, YANG Rui, SUN Jing-bo
. Determination of ethylene glycol, diethylene glycol, triethylene glycol, ethylene oxide and dioxane impurities in polysorbate 65/85 by GC[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(9)
: 1634
-1642
.
DOI: 10.16155/j.0254-1793.2022.09.17
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