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

Zhang, Lin; Yadav, Sandeep; Demeule, Barthélemy; Wang, Y. John; Mozziconacci, Olivier; Schöneich, Christian

doi:10.1007/s11095-016-2041-y

Cited by 54 publications

(42 citation statements)

References 47 publications

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“…This finding is consistent with a previous study, which showed that the degradation rate of di-and triesters of PEG sorbitan was much higher than that of monoesters in both PS80 and PS20. 14 Moreover, the relative abundance of non-esterified polyols seemed to be increased over time due to oxidative stress-induced ester scission 31 .…”

Section: Iron-induced Oxidative Degradation Of Ps80 Of Different Gradesmentioning

confidence: 99%

“…1,2 A PS subspecies assay is an attractive tool in identifying the PS degradation pathways based on changes of subspecies profile and can be utilized as part of investigation when PS content decreases in protein samples. It provides an overview of PS subspecies (Figure 1) by separating each subspecies based on hydrophobicity, in combination with universal detectors such as mass spectrometer, [31][32][33][34][35] CAD, 13,36,37 and ELSD. 34 The advantage of using a mass spectrometer as a detector is that it is capable of identifying both PS subspecies and degradants based on accurate mass measurement.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway

Liu

Jin

Menon

et al. 2022

Journal of Pharmaceutical Sciences

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Section: Iron-induced Oxidative Degradation Of Ps80 Of Different Gradesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway

Liu

Jin

Menon

et al. 2022

Journal of Pharmaceutical Sciences

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“…The stabilising properties of polysorbates in solution can be overshadowed by their susceptibility to autooxidation. The major sites for initiation of autooxidation for polysorbates include unesterified polyoxyethylenes [25], ester bonds [47] and the unsaturation sites of fatty acids [32,48]. Polysorbates are mixtures of various fatty acid esters.…”

Section: Polysorbates Degradation: Oxidation Of Polysorbates and Their Composition Profilesmentioning

confidence: 99%

Protein Formulations Containing Polysorbates: Are Metal Chelators Needed at All?

Brovč

Pajk

Šink³

et al. 2020

Antioxidants

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Proteins are prone to post-translational modifications at specific sites, which can affect their physicochemical properties, and consequently also their safety and efficacy. Sources of post-translational modifications include oxygen and reactive oxygen species. Additionally, catalytic amounts of Fe(II) or Cu(I) can promote increased activities of reactive oxygen species, and thus catalyse the production of particularly reactive hydroxyl radicals. When oxidative post-translational modifications are detected in the biopharmaceutical industry, it is common practice to add chelators to the formulation. However, the resultant complexes with metals can be even more damaging. Indeed, this is supported here using an ascorbate redox system assay and peptide mapping. Ethylenediaminetetraacetic acid (EDTA) addition strongly accelerated the formation of hydroxyl radicals in an iron-ascorbate system, while diethylenetriaminepentaacetic acid (DTPA) addition did not. When Fe(III) was substituted with Cu(II), EDTA addition almost stopped hydroxyl radical production, whereas DTPA addition showed continued production, but at a reduced rate. Further, EDTA accelerated metal-catalysed oxidation of proteins, and thus did not protect them from Fe-mediated oxidative damage. As every formulation is unique, justification for EDTA or DTPA addition should be based on experimental data and not common practice.

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“…Polysorbate materials are readily amenable to analysis by electrospray ionization (ESI; positive and negative) LC/MS as illustrated by the numerous recent publications, particularly from the biopharmaceutical industry, largely focusing on polysorbate stability. These range from more technique‐focused approaches, such as the use of radiolabeling and LC/MS and developing new multidimensional UHPLC/MS techniques to better characterize and monitor degradation in aqueous buffered formulations, through to the application of LC/MS to study degradation pathways. Such publications range from studies of potential degradation pathways for both Polysorbate 20 and Polysorbate 80 through to more specific investigations into the oxidative degradation of Polysorbate 80 and hydrolytic degradation of Polysorbate 20 and Polysorbate 80 .…”

Section: Results and Discussion By Techniquementioning

confidence: 99%

Challenges in polysorbate characterization by mass spectrometry

Penfield¹,

Rumbelow²

2020

Rapid Comm Mass Spectrometry

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Polysorbates are used in a variety of applications over a wide range of markets. Simple in concept, these products are complex in actual composition. Mass spectrometry and related techniques have been effectively used to characterize these products, from the major components to the minor residual production byproducts and degradation species. In this paper we review the use of MALDI‐MS, LC/MS, GC/MS, and SFC/MS in the analysis of these materials. The wealth of information provided by MALDI is presented, using Polysorbate 60 as an example. Limitations are described, with the impact of matrix selection and cationization agent demonstrated. Furthermore, unique challenges of MALDI analysis of Polysorbate 80 are shown. Polysorbates have been extensively analyzed, especially by the biopharmaceutical industry, to better understand the impact of various grades of purity and manufacture on the stability of formulations. Using Polysorbate 80 as an example, we illustrate some of the more advanced techniques used to more fully characterize these complex molecules using high‐resolution LC/MS and LC/MS/MS. Finally, the use of other techniques (such as GC/MS and SFC/MS) is briefly reviewed.

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

Abstract: The O-labeling technique and unique degradant patterns of all-laurate PS20 described here provide a direct approach to differentiate the types of PS degradation.

Cited by 54 publications

References 47 publications

Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway

Characterization of Polysorbate 80 by Liquid Chromatography-Mass Spectrometry to Understand Its Susceptibility to Degradation and Its Oxidative Degradation Pathway

Protein Formulations Containing Polysorbates: Are Metal Chelators Needed at All?

Challenges in polysorbate characterization by mass spectrometry

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