Volume 61, Issue 45 e202208854
Research Article

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

Gioacchino Luca Losacco

Corresponding Author

Gioacchino Luca Losacco

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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Raffeal Bennett

Raffeal Bennett

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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Imad A. Haidar Ahmad

Imad A. Haidar Ahmad

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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Rodell C. Barrientos

Rodell C. Barrientos

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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Jimmy O. DaSilva

Jimmy O. DaSilva

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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Yuyang Dong

Yuyang Dong

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA

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Alexander W. Schuppe

Alexander W. Schuppe

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA

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Zeshu Wang

Zeshu Wang

School of Chemistry, University of Bristol, Bristol, BS8 1TS USA

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Sheenagh Aiken

Sheenagh Aiken

School of Chemistry, University of Bristol, Bristol, BS8 1TS USA

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Ian Mangion

Ian Mangion

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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Varinder K. Aggarwal

Varinder K. Aggarwal

School of Chemistry, University of Bristol, Bristol, BS8 1TS USA

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Erik L. Regalado

Corresponding Author

Erik L. Regalado

Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA

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First published: 16 September 2022
Citations: 16

Graphical Abstract

A hybrid separation technique, referred to as Dual-Gradient Unified Chromatography (DGUC), enabling simultaneous multicomponent analysis of both small and large molecules across a wide polarity range is introduced. DGUC lays the foundation for the next generation of hybrid chromatographic techniques with the deployment of universal elution profiles obtained via multi-eluent blending beyond traditional separation modes.

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).

Conflict of interest

The authors declare no conflict of interest.

Data Availability Statement

The data that support the findings of this study are available in the supplementary material of this article.

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