Abstract
Rapid oxidation of polysorbate 80 in histidine buffer was observed upon brief exposure to stainless steel. LC/MS analysis indicates degradation of both polyoxyethylene sorbitan and polyoxyethylene head groups and unsaturated fatty acid chains, with further confirmation by RP-HPLC data. Both Fe2+ and Fe3+ were shown to induce polysorbate 80 oxidation. The degree of oxidation in polysorbate 20 and polysorbate 80 are comparable for the head groups and saturated fatty acid esters. However, the same phenomenon was not observed with placebo or drug product when containing an active at a threshold concentration, formulated in sodium citrate, in combination with histidine and sodium citrate, or with Na2 EDTA. Further, polysorbate 80 oxidation was not observed with Lilly's antibody containing the active, LY2951742, at or above a threshold concentration. Finally, no major polysorbate 80 degradation was observed in histidine buffer, with or without protein, in containers composed of glass or plastic, or when stainless steel exposure was otherwise completely absent. Finally, the 2-oxo oxidation form of histidine was not observed, but the other oxidation product and modifications of histidine were identified.
- Received September 25, 2017.
- Accepted December 11, 2017.
- Copyright © 2018, Parenteral Drug Association
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