THE MOLECULAR BASIS OF DRUG-PLASMA PROTEIN INTERACTION FOR CNS ACTIVE COMPOUNDS

The human serum albumin (HSA) is well known for its extraordinary binding capacity for both endogenous and exogenous compounds, including a wide range of drugs. The goal of our investigation was to evaluate the distribution process for 15 CNS active compounds. The drug-plasma protein interaction was evaluated under simulative physiological conditions on the HSA-based stationary phase by using the mixture of Sørensen phosphate buffer (pH 7.40) and acetonitrile modifier as a mobile phase (84:16 v/v). The retention parameters (k) were used to approximate the % of protein-binding by calculating the P(%) values. The results obtained through this study demonstrated that the constitutional properties (e.g. number of total bonds, atoms, carbon atoms) and lipophilicity have a strong positive impact on the HSA-binding affinity. The coefficient of diffusion has a negative impact, while the atoms and sites available for the CYP450 oxidation showed the most significant correlation (r = 0.92). This study provides a basis for further in vitro chromatographical investigations of drug-HSA interaction for CNS active compounds. The correlation between obtained retention data and the availability to enzymes oxidation indicates the application of the tested system in the assessment of the metabolic degradation profile of CNS related drugs.