Abstract A simple and precise high performance liquid chromatography method for concurrently determination of nilotinib (NTB) and carbamazepine (CBZ) in their pharmaceutical formulations was developed and validated. β-estradiol was used as an internal standard. The separation was carried out on Phenomenex Luna C18 RP-HPLC column using an isocratic elution at 1 mL/min flow rate with water- acetonitrile (30:70 v/v) mobile phase. Quantification was performed with a UV photodiode array detector at 286 nm. Solubility of NTB and CBZ was determined individually and their enhancing/reducing effect on solubility of each other in simulated biological fluids at various pHs was investigated. The calibration curves for each drug were linear in the range of 0.0125-5 µg/mL. The developed method was applied to pharmaceutical formulation successfully with no interfering peaks. The percentage recovery was 98.13% for CBZ and 96.25 % for NTB. It was observed that solubility of CBZ was increased in all in vitro interaction medium in the presence of NTB while solubility of NTB was increased mostly in pH 6.8 and slightly in pH 1.2.