Advances in LC platforms for drug discovery

Area of Science:

• Analytical Chemistry
• Medicinal Chemistry
• Pharmacology

Background:

• Liquid chromatography (LC) is crucial for identifying and characterizing potential drug lead compounds.
• Key applications include determining physico-chemical and pharmacokinetic properties of new entities.
• LC plays a vital role in both natural product and synthetic compound analysis.

Purpose of the Study:

• This review highlights recent advances in LC platforms over the last five years.
• It focuses on novel LC strategies for discovering bioactive molecules.
• The review examines the determination of lipophilicity, pKa, permeability, and metabolism.

Main Methods:

• Review of significant advances in LC instrumentation and column technology.
• Analysis of novel LC strategies for bioactive molecule discovery.
• Evaluation of techniques for determining drug properties like lipophilicity and metabolism.

Main Results:

• Improvements in LC instrumentation, columns, and detection enable ultra-fast and high-resolution separations.
• These advances address the challenges of high sample complexity and volume in early drug discovery.
• The review discusses the advantages and disadvantages of various LC strategies.

Conclusions:

• Liquid chromatography (LC) coupled with mass spectrometry is a powerful tool for drug discovery.
• Ultra-high pressure liquid chromatography (UHPLC) offers high-throughput and high-resolution analysis.
• These combined techniques are essential for modern drug discovery environments.