Unified chromatography in drug development: Exploiting chaotropic/kosmotropic salts for an accelerated method...

Area of Science:

• Analytical Chemistry
• Chromatography

Background:

• Supercritical fluid chromatography (SFC) has evolved with Unified Chromatography (UC), enabling transitions between supercritical and liquid states.
• UC offers combined benefits of SFC and liquid chromatography but requires simplified method development for industrial applications.

Purpose of the Study:

• To introduce a streamlined method development procedure for UC.
• To explore the impact of novel chaotropic/kosmotropic additives in SFC/UC.
• To demonstrate UC's utility in challenging separations and drug development.

Main Methods:

• Development of a novel, rapid method development protocol for UC.
• Investigation of mobile phase properties, including liquid modifier percentage and water content.
• Utilized additives like NaClO4 (chaotropic), HCOONa (kosmotropic), and NaOMs (mixed properties).

Main Results:

• Successful application of UC for separating nucleosides, nucleotides, indoles, triazoles, and related compounds.
• Demonstrated UC's effectiveness in analyzing an AbbVie pipeline compound under accelerated stability.
• UC with NaClO4 outperformed RP-HPLC in retaining and eluting degradation products.

Conclusions:

• Novel additives and a simplified procedure enhance UC's applicability in industrial drug development.
• UC provides a powerful tool for complex separations, offering advantages over traditional methods.
• UC, particularly with additives like NaClO4, shows significant promise for stability studies and impurity profiling.