• • Coupling pretreatments (coagulation, adsorption, biological oxidation) with ionizing radiation (IR) increased COD removal by 19%–42% and CTX removal by 8.4%–19% compared to direct IR at 5 kGy, demonstrating enhanced overall treatment efficiency.
• • Adsorption pretreatment using activated carbon reduced the matrix effect by 17%, the highest among the three pretreatments, while biological oxidation and coagulation sedimentation reduced it by 11% and 9%, respectively, indicating selective removal of radical scavengers.
• • Biological oxidation achieved the highest COD removal (47.3% after 12 h) but showed limited CTX removal (<20%), whereas coagulation with PFS removed 27.4% of COD but <2% of CTX, highlighting the need for process selection based on target pollutant and matrix composition.
• • The optimal conditions were: PFS as coagulant, activated carbon as adsorbent, and 6 h aeration for biological oxidation; these parameters are critical for scaling up pretreatment-IR systems for real pharmaceutical wastewater.