A review of polysorbate quantification and its degradation analysis by liquid chromatography coupled with charged aerosol detection

• Using charged aerosol detector (CAD) enables sensitive and accurate quantification of polysorbate (PS) analysis within complex formulations. • The consistency of CAD responses, combined with advanced LC, allows for the profiling of PS composition, facilitating the analysis of formulation stability. • The roles of hydrolysis and oxidation in PS degradation kinetics, influenced by pH, metal ions, and enzymatic activity, were analyzed with CAD. Polysorbates (PS), as non-ionic surfactants, contribute significantly to the stability of proteins in formulations. However, their lack of chromophore groups makes them difficult to detect with high sensitivity and simplicity. The charged aerosol detector (CAD) is an emerging and universal detector that can provide highly sensitive response signals to non-volatile or semi-volatile substances, such as esters, acids, oxidized aldehydes, and contaminant ions in PS. This article provides a comprehensive review of the qualitative and quantitative analysis of PS, profiling its composition, investigating the reasons for its degradation, and discussing its reaction mechanisms. This review aims to promote the quality control of PS production for the development of stable and safe protein formulations.