A Sensitive and High-Throughput LC-MSMS Method for Quantitation of Branched Polyethylenimine in Rat Plasma and Hepatocytes

Polyethyleneimine (PEI), a cationic polymer, has been widely studied as an efficient gene delivery carrier for various diseases. Unlike conventional small molecule compounds, PEI has variable molecular weights with repeating units composed of an amine group and two aliphatic carbons (-NHCH2CH2-) spacer. Such a structure means difficulty in the confirmation of the Q1 ion, and it also leads to serious non-specific binding (NSB) during sample extraction and analysis.

In this study, two matrices, rat plasma and hepatocytes, were selected as representatives to successfully develop a sensitive, high-throughput LC-MS/MS method for the quantification of branched PEI (bPEI) (~800 Da), which overcomes the challenges in chromatography, retention, and NSB issues.