A method for rapid screening of interactions of pharmacologically active compounds with albumin.

Abstract We determine the association constants for ligand–protein complex formation using the flow injection method. We carry out the measurements at high flow rates ( F  = 1 mL min −1 ) of a carrier phase. Therefore, determination of the association constant takes only a few minutes. Injection of 1 nM of the ligand (10 μL of 1 μM concentration of the ligand solution) is sufficient for a single measurement. This method is tested and verified for a number of complexes of selected drugs (cefaclor, etodolac, sulindac) with albumin (BSA). We obtain K  = 4.45 × 10 3  M −1 for cefaclor, K  = 1.00 × 10 5  M −1 for etodolac and K  = 1.03 × 10 5  M −1 for sulindac in agreement with the literature data. We also determine the association constants of 20 newly synthesized 3β- and 3α-aminotropane derivatives with potential antipsychotic activity – ligands of 5-HT 1A , 5-HT 2A and D 2 receptors with the albumin. Results of the studies reported here indicate that potential antipsychotic drugs bind weakly to the transporter protein (BSA) with K  ≈ 10 2 –10 3  M −1 . Our method allows measuring K in a wide range of values (10 2 –10 9  M −1 ). This range depends only on the solubility of the ligand and sensitivity of the detector.