Rational construction of MOF-on-MOF multifunctional adsorbent for MSPE of various additives and their degradation products in plastic packaging materials and large-volume parenteral preparations

The widespread clinical use of large-volume parenteral preparations (LVP) has raised serious concerns about the migration of additives and their degradation products from plastic packaging into LVP. The simultaneous migration of multiple additives exacerbates the toxic risks of combined exposure. However, simultaneous monitoring of multiple compounds in such complex matrices remains challenging. Here, a novel magnetic solid phase extraction (MSPE) coupled with ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed for the enrichment and determination three plasticizers, four UV stabilizers, five antioxidants, and degradation products in both plastic packaging and LVP. The MSPE adsorbent, a newly fabricated MOF-on-MOF composite designated MIL-88 A(Fe)-500C@ZIF-8-2, was prepared via carbonization followed by surfactant-assisted growth. It exhibited a high specific surface area (1043 m 2 ·g −1 ), a hierarchical pore structure (micropores of 1.88 nm and mesopores of 3.49/13.14 nm), abundant functional groups, and excellent hydrophobicity (contact angle 137.8°), which collectively enabled efficient multisite synergistic adsorption. Key extraction parameters were optimized, yielding optimal conditions of 15 mg adsorbent, 10 min adsorption (without pH adjustment), and elution with 1.5 mL acetonitrile for 10 min. Under the optimized conditions, the method demonstrated good linearity ( r  > 0.99), low detection limits (0.03–1.1 ng·g −1 for infusion bottle, 0.03–1.3 ng·g −1 for infusion bag, and 1.2–31.0 ng·L −1 for LVP), high accuracy (71.4–98.6%), and precision (RSD < 9.1%). Multiple additives were detected in actual packaging and LVP samples. Adsorption experiments revealed that the adsorption process was well described by the pseudo-second-order and Langmuir isotherm models. The adsorption behavior likely involved synergistic effects of multiple intermolecular interactions, including hydrophobic forces, π-π interactions, hydrogen bonding, and weak electrostatic interactions. This work provided a powerful analytical tool for safeguarding drug quality and a versatile material platform for the extraction of trace contaminants from complex matrices.