Unraveling excretion behavior of polyethylene glycol 1000 with 13-26 subunits in rats by UHPLC-MS/MS

This study established a robust and selective ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) method to investigate the excretion behavior of polyethylene glycol 1000 (PEG1K) oligomers (N = 13–26) in rats. PEG is widely used in pharmaceutical applications, particularly in drug delivery systems, yet detailed excretion profiles of lower molecular weight PEGs remain insufficiently characterized. The developed method utilized ammonium adducts ([M+NH₄]⁺) as precursor ions in multiple reaction monitoring mode, enabling sensitive and high-throughput quantification of individual oligomers in biological matrices. Following intravenous administration in rats, excretion kinetics were monitored over 48   hours. Cumulative recovery analysis revealed that renal excretion was the dominant elimination pathway, accounting for 47.30–68.52% of the administered dose in urine, while fecal excretion represented only 0.66–3.38%. These findings provide critical insights into the in vivo disposition of PEG1K, supporting its safety evaluation and rational application in drug formulation. The presented analytical platform offers a reliable tool for polymer pharmacokinetic studies.