A fast and green UPCC-MS/MS method for analyzing the tissue distribution of polyethylene glycol polymers (7-20 subunits) in zebrafish.

The structural heterogeneity and environmental persistence of polydisperse polymers, such as polyethylene glycol (PEG), complicate accurate ecological risk assessment. Conventional analytical techniques often suffer from inadequate sensitivity or excessive solvent consumption when analyzing complex biological matrices, hindering the precise quantification of individual oligomers. Herein, we report a high-throughput, sustainable analytical framework utilizing ultra-performance convergence chromatography-tandem mass spectrometry (UPCC-MS/MS) to characterize the toxicokinetic and spatiotemporal tissue distribution of PEG oligomers (7-20 subunits) in a zebrafish model. Leveraging supercritical CO2 as the mobile phase, we achieved baseline resolution for 14 distinct oligomers within a 3.1-minute run time, significantly enhancing analytical throughput. To ensure robust quantification, the platform integrates synchronized post-column compensation with ammonium adduct monitoring, yielding a four-fold improvement in sensitivity for trace-level detection. In vivo investigations revealed a distinct "chain-length-dependent" accumulation pattern, with the intestine identified as the primary reservoir, providing critical insights into the biological transport and sequestration of polydisperse polymers. Furthermore, the method's operational feasibility and ecological footprint were rigorously validated using a tripartite framework consisting of Analytical GREEnness (AGREE), Blue Applicability Grade Index (BAGI), and Greenness Evaluation Metric for Analytical Methods (GEMAM) metrics, confirming its superior sustainability. This work offers a robust, green paradigm for the bioanalysis of complex polymers in aquatic ecosystems.