Development of Relatively Simple Sample Pretreatment Strategies to Selectively Remove Chromatographic Interfering Peaks of Polysorbate 80 from Liquid Oral Finished Drug Product

Abstract Polysorbate 80 (PS 80) is a nonionic surfactant, used in myriad of pharmaceutical, food and cosmetic formulations. PS 80 components have strong UV absorbance and retain under reversed-phase chromatographic conditions, significantly masking sections of the chromatogram. PS 80-related peaks interferences in a sample are common and can be difficult to separate from the analyte peaks. A liquid oral finished product (LOFP) containing PS 80 and Ivermectin as the active pharmaceutical ingredient (API) was selected for this study. Herein, we report two sample pretreatment strategies focusing on the selective removal of PS 80 from the LOFP. Both methods significantly reduce and/or practically eliminate excipients and PS 80-related peaks interferences from the LOFP without a negative impact on the API and its key-related substances recovery. The solid-phase extraction (SPE) strategy uses a C18 SPE followed by a silica gel SPE, whereas the liquid–liquid extraction strategy uses in situ-generated sodium caprylate for the removal of formulation excipients and PS 80. These methods can significantly increase the reliability of high-performance liquid chromatography methods and decrease false positive out-of-specifications events because of coelution of PS 80-related peaks with peaks of interest.