Unraveling the cytotoxicity and cellular uptake of low, medium and high molecular weight polyethylene glycol polymers in MCF-7 cells by green UPLC-MS/MS methods.

Unraveling the cytotoxicity and cellular uptake of low, medium and high molecular weight polyethylene glycol (PEG) in cells is important for evaluation of therapeutic efficacy and toxicity of PEGylated drug delivery systems. In this study, cellular uptake of PEG600, PEG2K, PEG4K and PEG10K in MCF-7 cells was first studied by an UPLC-MS/MS assay coupled with collision induced dissociation (CID) in source technique. The CID of PEG in source with high values of declustering potentials generates numerous PEG-related product ions. These PEG-related fragment ions can be further broken into specific product ions in the collision cell as alternative ions for detection of PEG. The quantification of PEG was finally performed with the MRM transition (m/z 221.0 → 89.0). The experimental results indicated that the toxicity of PEG600, PEG2K, PEG4K and PEG10K was not significant at concentrations of 5-1200 μg/mL and the amounts of PEG polymers entry into MCF-7 cells at was small. The greenness of the developed analytical methods was also assessed by Analytical Eco-Scale, Analytical Greenness calculator (AGREE) and Green Analytical Procedure Index (GAPI) in this study.