Quantitative recovery of methoxy poly(ethylene glycol) and PEGylated nanosystems from complex biological matrices

This study systematically screened deproteinization conditions for the selective and quantitative recovery of methoxy poly(ethylene glycol) (mPEG) and model PEGylated nanomedicines, either intact or as mPEG components, from full human serum and full rat liver lysate. Although mPEG and all PEGylated nanosystems were a priori soluble under all the deproteinization conditions investigated, their recovery from serum (as measured by the barium-iodide assay and/or ¹H NMR spectroscopy) varied considerably depending on the agent employed. Surprisingly, acetonitrile (with or without acidic pre-treatment) was found to be the only broadly applicable agent for the reliable, selective, and quantitative recovery of mPEG and PEGylated nanosystems from both serum and liver lysate. With very few exceptions, neither the molecular characteristics of mPEG nor the composition of the nanosystems significantly influenced recovery under these conditions.