Tutorial on modelling chromatographic surrogation of biological processes

Abstract

The accurate emulation of biological partition systems through physicochemical models is crucial in pharmacology, toxicology, and environmental science for understanding the ADMET profiles of substances. Direct experimentation on biological systems can be long, expensive, and ethically and practically challenging, so developing reliable physicochemical models is essential. These models help predict compound behaviour in organisms, reduce animal testing, and streamline drug discovery and risk assessment. Chromatographic systems are of particular interest to mimic biological or environmental processes because of its versatility, as they provide a large number of different partition systems only by changing the nature of the mobile and stationary or pseudostationary phases. The effectiveness of any physicochemical system in emulating biological processes is usually evaluated through empirical correlation with biological data. However, the characterization of physicochemical and biological systems using a common model, such as Abraham's solvation model, allows to identify the best physicochemical systems to surrogate particular biological or environmental processes, only by comparison of the system constants of the models. This tutorial demonstrates how to compare, predict, and improve the efficiency of physicochemical systems to surrogate biological or environmental ones without the need for previous empirical correlations. Skin permeation is presented as example of chromatographic surrogation and case study.

Keywords

• Chromatographic surrogation, Linear free energy relationships
• Abraham's solvation model
• Euclidean distances
• Principal component analysis
• Skin permeation