title: NMR method for accurate quantification of polysorbate 80 copolymer composition.
abstract: (13)C NMR spectroscopic integration employing short relaxation delays and a 30° pulse width was evaluated as a quantitative tool for analyzing the components of polysorbate 80. (13)C 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 (13)C 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 (13)C 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.
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Aifa
authors.initials: A
authors.lastname: Wang
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Meng
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Ning
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Huaxin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Chinese Pharmaceutical Association, Jianwai SOHO 9-1801 , No. 4 Jianwai Street, Chaoyang District, Beijing 100022, China.
authors.forename: Lixia
authors.initials: L
authors.lastname: Ding
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Xiao
authors.affiliation: National Institute of Food and Drug Control , No. 2 Tiantan Xili, Chongwen District, Beijing 100050, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
mesh_terms: D004952:Esters / Q000032:analysis; D007547:Isosorbide / Q000032:analysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019301:Oleic Acid / Q000032:analysis; D011092:Polyethylene Glycols / Q000032:analysis; D058105:Polymerization; D011136:Polysorbates / Q000737:chemistry*
chemical_list: D004952:Esters; D011136:Polysorbates; D019301:Oleic Acid; D011092:Polyethylene Glycols; D007547:Isosorbide