Efficient Determination of β-Agonists in Environmental Water and Animal-Derived Matrices by NH2-UiO-66 Based d-SPE Coupled with UPLC-MS/MS: Performance, Mechanism and Application

β-agonists are prohibited antibiotics that have raised concerns due to their illegal use in the livestock industry, posing potential toxicity risks to human health. For ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) analysis of β-agonists, effective sample pretreatment is a crucial and challenging process that dictates the overall reliability and sensitivity of the method. Thus, this study developed a reliable method utilizing dispersive solid-phase extraction (d-SPE) with NH2-UiO-66 as a superior adsorbent, coupled with UPLC-MS/MS, to extract and quantify β-agonists in environmental water, swine urine, and milk. The synthesized NH2-UiO-66 exhibited outstanding adsorption capacities (146.06–358.00 mg/g) towards the target analytes. The optimized method demonstrated excellent performance: low matrix effects (−13.10–15.30%), wide linearity (0.1–50 μg/L), low limits of detection (0.04–0.09 μg/L), and satisfactory recoveries (81.48–106.67%) with good precision (intra-day RSDs 1.51–6.24%; inter-day RSDs 2.06–10.96%). Adsorption mechanism studies revealed that the extraction process, which followed the Langmuir isotherm and pseudo-second-order kinetic models, was driven primarily by electrostatic interactions, π-π stacking, and hydrogen bonding. Moreover, the material could be reused up to 10 times, with satisfactory recoveries of 81.30% to 116.10%. The proposed NH2-UiO-66-d-SPE-UPLC-MS/MS protocol is generic and provides a robust and practical solution for monitoring trace β-agonists in animal-derived foods and environmental samples, ensuring food safety and environmental health.