Liquid chromatography in determination of pharmacokinetic properties of compounds in drug discovery process

Abstract

Liquid chromatography plays a pivotal role in the determination of pharmacokinetic properties during drug discovery, particularly through the evaluation of lipophilicity. This parameter is essential in drug development, significantly influencing pharmacokinetic and pharmacodynamic behavior of potential drugs. It affects membrane permeability, solubility, distribution, and interaction with biological targets, making it a central focus in the early stages of drug design. Poor lipophilicity-related characteristics are often associated with drug failures, inefficacy, toxicity, and increased development costs. Experimental and computational methods, such as chromatographic techniques and theoretical calculations, are vital for accurately determining lipophilicity. These approaches enable the simulation of biological processes, providing insights into how lipophilicity impacts ADME (absorption, distribution, metabolism, and excretion) properties and supporting the optimization of drug candidates. In silico tools further enhance the efficiency of ADME evaluations, reducing the risk of pharmacokinetic-related failures and streamlining the drug discovery process.