A reliable method using disposable pipette extraction (DPX) based on composite of pernigraniline and styrenedivinylbenzene (Sty-DVB) copolymer was applied to the analysis of dexamethasone in synovial fluid using highperformance liquid chromatography and ultraviolet (UV) detector (HPLC-UV). DPX variables, namely, number of draw/eject cycles for extraction or desorption, sample pH, volume, and desorption solvent, were optimized to establish the best sorption equilibrium and analysis time. The highest extraction efficiency value was obtained with 50 μL of synovial fluid mixed with 1950 μL of water, in five cycles of 300 μL of sampling, followed by liquid desorption of the drug with 300 μL of methanol in three cycles. The developed method demonstrated a linear response over the range from 10 to 100 ng/mL, with R 2 = 0.993. The limit of quantification (LOQ) was 10 ng/mL. Based on the validation results, the proposed method can be a useful tool to detect dexamethasone levels in synovial fluid.