Ultrasensitive and Tracking of C-Labeled PEG-PLA Degradation Products by MALDI-TOF Mass Spectrometry

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 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 C-labeled PEG-PLA copolymers, combined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), to monitor their and degradation. Incorporating C 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 C-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 tracking and elucidation of fate of this widely investigated polymer family.