Mechanistic understanding of metal-catalyzed oxidation of polysorbate 80 and monoclonal antibody in biotherapeutic formulations

Detailed profiling of polysorbate 80 oxidative degradation products and hydrolysates using liquid chromatography–tandem mass spectrometry analysis

“…However, commercially available polysorbate products contain substantial amounts of byproducts, and various analytical methods have been developed for their detection. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] PS80 is known to be oxidatively or enzymatically degraded, and the degradation of PS80 can sometimes affect protein stability. 3,7,8,[24][25][26] Therefore, polysorbate degradation has emerged as a major challenge in the biopharmaceutical community.…”

“…Several studies have reported the stability and degradation products of polysorbate. [7][8][9][10][11][12][13][14][15][16] However, because PS80 is a complex mixture comprising many constituents, comprehensive evaluations of its degradation, especially with respect to oxidative degradation products, are difficult and insufficient. The decrease in PS80 components and the increase in its degradation products were evaluated by total ion chromatography [7][8][9][10][11][12] or charged aerosol detection.…”

“…The decrease in PS80 components and the increase in its degradation products were evaluated by total ion chromatography [7][8][9][10][11][12] or charged aerosol detection. [13][14][15][16] Liu et al reported two oxidative degradation pathways and six degradation products (hydroxy-C18:1, epoxy-C18:0, keto-C18:1, hydroperoxy-C18:1, oxo-C9:0, and 2-decenedioic acid ester) of PS80. 7 The structural formula of each degradation product and the difference in molecular weight from the oleate ester are shown in Figure S1.…”

Profiling polysorbate 80 components using comprehensive liquid chromatography–tandem mass spectrometry analysis

“…Recently, polysorbate degradation has emerged as a major challenge in the biopharmaceutical community, and several studies have reported the stability and degradation products of polysorbate 2,9,14–22 . Thus, there is an immediate need to establish reliable polysorbate analysis methods throughout pharmaceutical processes, including development, formulation, stabilization, and quality control.…”

“…4,[7][8][9][11][12][13][14][15][16] This discrepancy is because POE-IS-esters are linear bifunctional molecules that can accommodate two rather than Recently, polysorbate degradation has emerged as a major challenge in the biopharmaceutical community, and several studies have reported the stability and degradation products of polysorbate. 2,9,[14][15][16][17][18][19][20][21][22] Thus, there is an immediate need to establish reliable polysorbate analysis methods throughout pharmaceutical processes, including development, formulation, stabilization, and quality control. Due to the inherent heterogeneity of polysorbates and the absence of a universal reference for different components, the development and validation of quantification methods for polysorbates can be challenging.…”