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

Gioacchino Luca Losacco, Raffeal Bennett, Imad A. Haidar Ahmad, Rodell C. Barrientos, Jimmy O. Dasilva, Yuyang Dong, Alexander W. Schuppe, Zeshu Wang, Sheenagh Aiken, Ian Mangion, Varinder K. Aggarwal, Erik L. Regalado

Research output: Contribution to journalArticle (Academic Journal)peer-review

13 Citations (Scopus)

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. 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).
Original languageEnglish
Article numbere202208854
JournalAngewandte Chemie - International Edition
Volume61
Issue number45
Early online date16 Sept 2022
DOIs
Publication statusE-pub ahead of print - 16 Sept 2022

Bibliographical note

Funding Information:
The authors would like to thank Prof. Stephen L. Buchwald for insightful discussion and asymmetric catalysis support. We also thank Dr. Peter Ratsep for his input on the SFC system. The MRL Postdoctoral Research Fellow Program is acknowledged for financial support provided by a fellowship (G. L. L.). Research reported in this publication was also supported by the Arnold and Mabel Beckman Foundation for a postdoctoral fellowship (A. W. S.) and the National Institutes of Health (R35‐GM122483).

Publisher Copyright:
© 2022 Wiley-VCH GmbH.

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