(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.
This article concerns the development and co-validation of a porcine insulin (pINS) certified reference material (CRM) produced by the National Institute of Metrology, People's Republic of China. Each CRM unit contained about 15 mg of purified solid pINS. The moisture content, amount of ignition residue, molecular mass, and purity of the pINS were measured. Both high-performance liquid chromatography-isotope dilution mass spectrometry and a purity deduction method were used to determine the mass fraction of the pINS. Fifteen units were selected to study the between-bottle homogeneity, and no inhomogeneity was observed. A stability study concluded that the CRM was stable for at least 12 months at -20 °C. The certified value of the CRM was (0.892 ± 0.036) g/g. A co-validation of the CRM was performed among Chinese, Japanese, and Korean laboratories under the framework of the Asian Collaboration on Reference Materials. The co-validation results agreed well with the certified value of the CRM. Consequently, the pINS CRM may be used as a calibration material or as a validation standard for pharmaceutical purposes to improve the quality of pharmaceutical products.
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