Determining the Oxidation Mechanism through Radical Intermediates in Polysorbates 80 and 20 by Electron Paramagnetic...

Polysorbates 20 and 80 (PS20 and PS80) are added to many commercial biologic and vaccine pharmaceuticals. It is commonly known that these polysorbates undergo a radical oxidation mechanism; however, the identity of these radical intermediates has not been clearly determined. Furthermore, PS20 and PS80 differ by the presence of a lauric acid instead of an oleic acid, respectively. The oxidation of PS80 is thought to be centered around the double bond of the oleic acid even though PS20 also undergoes oxidation, making the mechanism of oxidation unclear for PS20. Using commercial stocks of PS20 and PS80 alkyl (R^•), alkoxyl (C-O^•) and peroxyl (C-OO^•) radicals were detected by electron paramagnetic resonance spectroscopy likely originating from radical-initiating species already present in the material. When dissolved in water, the peroxyl radicals (C-OO^•) originally in the stocks were not detected but poly(ethylene oxide) radicals were. An oxidative pathway for polysorbates was suggested based on the radical species identified in the polysorbate stock material and solutions.