Herein, a new extraction mode of classical fabric phase sorptive extraction (FPSE), namely mixed-mode strong cation exchanging FPSE is presented and evaluated for the first time for the determination of tetracycline residues in milk, after protein precipitation. FPSE is a microextraction technique characterized by high chemically stable sorbent, higher analyte retention capacity and faster analyte diffusion capability, where the target analytes interact with the extraction sorbent during the pre-treatment process via a plethora of intermolecular/interionic interactions exerted by different functional moieties implanted on the sponge-like porous sol–gel sorbent network. Subsequently, the selectively retained analytes are eluted using a small volume of solvent system. A novel extraction membrane containing sol–gel C₁₈/propyl sulfonic acid, a mixed mode sorbent consisting of neutral, C₁₈ and strong cation exchanger, propyl sulfonic acid (C₃H₆SO₃⁻) coated on 100% cotton cellulose fabric substrate was designed, synthesized, characterized and evaluated for the selective isolation of four tetracycline antibiotic residues from milk samples.

For quantitative analysis, high performance liquid chromatography coupled with a UV detector (at 350 nm) was used. The method was validated according to the 2002/657/EC decision with regards to linearity, selectivity, stability, limits of detection and quantitation (LOD/LOQ), decision limit, detection capability, trueness, precision and ruggedness, according to the Youden’s test. Recoveries ranged between 88.9 and 122.4%, while the LOD and LOQ were obtained at 15 μg kg⁻¹ and 50 μg kg⁻¹, respectively. Finally, the composite analytical method was applied to monitor the presence of residual tetracyclines in milk samples purchased from a local Greek market.