Dual-Gradient Unified Chromatography: A New Paradigm for Versatility in Simultaneous Multicomponent Analysis

Angew Chem Int Ed Engl. 2022 Nov 7;61(45):e202208854. doi: 10.1002/anie.202208854. Epub 2022 Oct 7.

Abstract

Generality in analytical chemistry can be manifested in impactful platforms that can streamline modern organic synthesis and biopharmaceutical processes. We herein introduce a hybrid separation technique named Dual-Gradient Unified Chromatography (DGUC), which is built upon an automated dynamic modulation of CO2 , organic modifier, and water blends with various buffers. This concept enables simultaneous multicomponent analysis of both small and large molecules across a wide polarity range in single experimental runs. After a careful investigation of its fundamental aspects, a DGUC-DAD-MS screening workflow that combines multiple orthogonal column and mobile phase choices across a far-reaching universal elution profile is also reported. The power of this framework is demonstrated with new analytical applications guiding academic and industrial laboratories in the development of new (bio)pharmaceutical targets (e.g. synthetic intermediates, nucleosides, cyclic and linear peptides, proteins, antibody drug conjugates).

Keywords: Analytical Methods; Asymmetric Reactions; Chromatography; Multicomponent analysis; Total Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Chromatography*
  • Nucleosides
  • Peptides
  • Proteins* / analysis
  • Water / chemistry

Substances

  • Proteins
  • Peptides
  • Water
  • Nucleosides