Degradation Mechanisms of Polysorbate 20 Differentiated by 18O-labeling and Mass Spectrometry

Autor: Barthélemy Demeule, Lin Zhang, Christian Schӧneich, Olivier Mozziconacci, Sandeep Yadav, Y. John Wang
Rok vydání: 2016
Předmět:
Zdroj: Pharmaceutical Research. 34:84-100
ISSN: 1573-904X
0724-8741
Popis: To investigate the mechanisms of polysorbate (PS) degradation with the added objective of differentiating the hydrolysis and oxidation pathways. Ultra-performance liquid chromatography mass spectrometry (UPLC-MS) was utilized to characterize all-laurate polysorbate 20 (PS20) and its degradants. 18O stable isotope labeling was implemented to produce 18O-labeled degradation products of all-laurate PS20 in H2 18O, with subsequent UPLC-MS analysis for location of the cleavage site on the fatty acid-containing side chain of PS20. The analysis reveals that hydrolysis of all-laurate PS20 leads to a breakdown of the ester linkage to liberate free lauric acid, showing a distinct dependence on pH. Using a hydrophilic free radical initiator, 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) to study the oxidative degradation of all-laurate PS20, we demonstrate that free lauric acid and polyoxyethylene (POE) laurate are two major decomposition products. Measurement of 18O incorporation into free lauric acid indicated that hydrolysis primarily led to 18O incorporation into free lauric acid via “acyl-cleavage” of the fatty acid ester bond. In contrast, AAPH-exposure of all-laurate PS20 produced free lauric acid without 18O-incorporation. The 18O-labeling technique and unique degradant patterns of all-laurate PS20 described here provide a direct approach to differentiate the types of PS degradation.
Databáze: OpenAIRE
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