The Degradation of Polysorbates 20 and 80 and its Potential Impact on the Stability of Biotherapeutics

Abstract

Although some degradants can potentially influence the stability of the protein (as discerned from spiking studies), degradation of polysorbates did not impact the stability of the different proteins tested in pharmaceutically relevant temperature and storage conditions.

Searching for Life on Mars: Degradation of Surfactant Solutions Used in Organic Extraction Experiments

“…They are chemically diverse mixtures containing sorbitan polyoxyethylene esters of fatty acids, along with substantial amounts of polyoxyethylene, sorbitan polyoxyethylene, and isosorbide polyoxyethylene fatty acid esters (Ayorinde et al, 2000;Frison-Norrie and Sporns, 2001;Kishore et al, 2011a). Polysorbates are well known to be vulnerable to degradation.…”

“…Autoxidation produces peroxides, aldehydes, acids, ketones, n-alkanes, and fatty acid esters via radical initiation, propagation, and termination reactions (Kerwin, 2008;Kishore et al, 2011b). Autoxidation can be slowed by measures that prevent radical initiation, such as excluding peroxides, heat, light, and oxygen (Yao et al, 2009;Kishore et al, 2011a), or the addition of an antioxidant such as butylated hydroxytoluene (Donbrow, 1987), while removing transition metal ions such as copper can also reduce catalytic effects (Kerwin, 2008). Hydrolysis, which can be both acid-and base-catalyzed (Bates et al, 1973), produces fatty acids (Kerwin, 2008).…”

“…This suggests that Zonyl FS-300 would be more stable at elevated temperatures, relative to PS80. Autoxidation of ethylene oxide units in Zonyl FS-300 will likely produce species comparable to those produced by the autoxidation of ethylene oxide units in PS80 (Kishore et al, 2011a). The fluorocarbon chain in Zonyl FS-300 is rather inert and resistant to degradation.…”

“…Oxidation can proceed directly via reaction with dissolved or headspace oxygen or via autoxidation of ethylene oxide units (Donbrow, 1987;Yao et al, 2009;Kishore et al, 2011a). The oxygen content of the solutions was minimized via degassing of solvent and purging the headspace of the sample bottles with nitrogen.…”

“…It is therefore important that the surfactant chosen does not include impurities or produce degradation products sufficiently similar to biomarkers that cross-reaction with the antibodies can result in false positives. It is well known that commercially available PS80 is an impure mixture, containing abundant contaminants including isosorbide polyoxyethylene fatty acid esters (Ayorinde et al, 2000;Frison-Norrie and Sporns, 2001;Kishore et al, 2011a), the presence of which may be able to induce a false-positive detection of organic matter in a martian sample via crossreactivity with biomarkers. While purification of a surfactant to remove troublesome contaminants on Earth can be addressed during construction of such an instrument, the problem of degradation of the surfactant en route to Mars is more challenging.…”