NMR Method for Accurate Quantification of Polysorbate 80 Copolymer Composition

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• 作者：Qi Zhang ; Aifa Wang ; Yang Meng ; Tingting Ning ; Huaxin Yang ; Lixia Ding ; Xinyue Xiao ; Xiaodong Li
• 刊名：Analytical Chemistry
• 出版年：2015
• 出版时间：October 6, 2015
• 年：2015
• 卷：87
• 期：19
• 页码：9810-9816
• 全文大小：309K
• ISSN：1520-6882

文摘

¹³C NMR spectroscopic integration employing short relaxation delays and a 30掳 pulse width was evaluated as a quantitative tool for analyzing the components of polysorbate 80. ¹³C NMR analysis revealed that commercial polysorbate 80 formulations are a complex oligomeric mixture of sorbitan polyethoxylate esters and other intermediates, such as isosorbide polyethoxylate esters and poly(ethylene glycol) (PEG) esters. This novel approach facilitates the quantification of the component ratios. In this study, the ratios of the three major oligomers in polysorbate 80 were measured and the PEG series was found to be the major component of commercial polysorbate 80. The degree of polymerization of -CH₂CH₂O- groups and the ratio of free to bonded -CH₂CH₂O- end groups, which correlate with the hydrophilic/hydrophobic nature of the polymer, were analyzed, and were suggested to be key factors for assessing the likelihood of adverse biological reactions to polysorbate 80. The ¹³C NMR data suggest that the feed ratio of raw materials and reaction conditions in the production of polysorbate 80 are not well controlled. Our results demonstrate that ¹³C NMR is a universal, powerful tool for polysorbate analysis. Such analysis is crucial for the synthesis of a high-quality product, and is difficult to obtain by other methods.