<p>Melperone and tiapride are antipsychotic agents frequently used in combination for the treatment of delirium. This combination is commonly prescribed, including in patients undergoing hemodialysis, yet pharmacokinetic data in this population are scarce despite the likelihood of altered drug elimination due to impaired renal function. To support future pharmacokinetic studies and therapeutic drug monitoring in hemodialysis patients, a UHPLC-MS/MS method was developed and validated for the simultaneous quantification of melperone and tiapride in human serum and dialysate. The method showed excellent linearity over the range of 0.3–1250&#xa0;ng&#xa0;cm⁻³ for both analytes. It achieved high accuracy (relative error within ± 12%) and precision (RSD ≤ 10.3%) in both matrices, with acceptable matrix effects and recoveries ≥ 94%. The method complies with current bioanalytical validation standards and is well suited for clinical pharmacokinetic applications in patients with renal impairment.</p> Graphical Abstract <p></p>