A new thin film was fabricated using Fe3O4@SiO2-polyoxometalate (POM) as the coating and it was coupled with a HPLC-UV to develop a method for the selective determination of ibuprofen, paracetamol and diclofenac (as the model analytes) from human plasma and urine samples. The prepared magnetic POM was coated on the pores and surface of cotton yarn to prepare the extracting device. The prepared sorbent was characterized by several techniques including: FT-IR, XRD, BET, SEM, and VSM analysis. Using a multivariate optimization strategy (Plackett-Berman design (PBD) and Box-Behnken Design (BBD)), extraction factors were optimized. The optimal condition is: pH=4, extraction time=23 min, desorption time=3 min, desorption volume=400 µL, and Na2SO4 concentration=0.8 %. In the optimal condition, the linearity of the method was in the range of 0.5–200 µg l-1. LODs, LOQs, and intra-day as well as inter-day RSDs were <0.24 µg L−1, 0.81 µg L−1, and 4.1 %, respectively. The enrichment factor (EF) values for the tested substances varied from 16 to 21. The absolute recoveries (ARs%) were also between 64 and 84 %. The sorbent extracted the analytes up to 32 times with little changes in the ER (95 ± 1.5). This method was successfully applied to detect target analytes in biological fluids, achieving high recovery. This novel approach combines efficiency with practicality, making it well-suited for field applications. In addition, the greenness and whiteness of the method (sustainability assessment) were evaluated using the qualitative green assessment tools including AGREE, BAGI and the white analytical chemistry assessment tool (RGB12). The high BAGI (72.5) and RGB 12 (94.7) scores confirmed the method's strong applicability, cost-effectiveness, and sustainability
