Abstract
Copolymers of poly(lactic acid) (PLA) and poly-(ethylene glycol) (PEG) are widely used in biomedical applications. As inactive ingredients in formulations, tracking their degradation byproducts in vivo stands as a major challenge but is a pivotal endeavor to ensure safety and further progress in clinical stages. Current bioanalytical methods used to monitor this degradation lack sensitivity and quantification precision. This study introduces a cost-effective synthetic route for 13C-labeled PEG−PLA copolymers, combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), to monitor their in vitro and ex vivo degradation. Incorporating 13C isotopes into copolymers significantly enhances MALDI-TOF sensitivity, allowing for precise detection of degradation products at exceedingly low concentrations. We demonstrate the ability to trace 13C-labeled PEG−PLA in complex biological media (urine, plasma) at concentrations 100 times lower than labeled PEG−PLA. Our results pave the way toward ultrasensitive in vivo tracking and elucidation of in vivo fate of this widely investigated polymer family.