Dual-Gradient Unified Chromatography: A New Paradigm for Versatility in Simultaneous Multicomponent Analysis
Corresponding Author
Gioacchino Luca Losacco
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorRaffeal Bennett
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorImad A. Haidar Ahmad
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorRodell C. Barrientos
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorJimmy O. DaSilva
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorYuyang Dong
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorAlexander W. Schuppe
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorZeshu Wang
School of Chemistry, University of Bristol, Bristol, BS8 1TS USA
Search for more papers by this authorSheenagh Aiken
School of Chemistry, University of Bristol, Bristol, BS8 1TS USA
Search for more papers by this authorIan Mangion
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorVarinder K. Aggarwal
School of Chemistry, University of Bristol, Bristol, BS8 1TS USA
Search for more papers by this authorCorresponding Author
Erik L. Regalado
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorCorresponding Author
Gioacchino Luca Losacco
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorRaffeal Bennett
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorImad A. Haidar Ahmad
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorRodell C. Barrientos
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorJimmy O. DaSilva
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorYuyang Dong
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorAlexander W. Schuppe
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139 USA
Search for more papers by this authorZeshu Wang
School of Chemistry, University of Bristol, Bristol, BS8 1TS USA
Search for more papers by this authorSheenagh Aiken
School of Chemistry, University of Bristol, Bristol, BS8 1TS USA
Search for more papers by this authorIan Mangion
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorVarinder K. Aggarwal
School of Chemistry, University of Bristol, Bristol, BS8 1TS USA
Search for more papers by this authorCorresponding Author
Erik L. Regalado
Analytical Research and Development, MRL, Merck & Co., Inc., Rahway, NJ 07065 USA
Search for more papers by this authorGraphical 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.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.
Filename | Description |
---|---|
anie202208854-sup-0001-Graphical_abstract_V3.tif887.6 KB | Supporting Information |
anie202208854-sup-0001-misc_information.pdf1 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1
- 1aL. Urquhart, Nat. Rev. Drug Discovery 2022, https://doi.org/10.1038/d41573-021-00211-7;
- 1bD. A. DiRocco, Y. Ji, E. C. Sherer, A. Klapars, M. Reibarkh, J. Dropinski, R. Mathew, P. Maligres, A. M. Hyde, J. Limanto, A. Brunskill, R. T. Ruck, L.-C. Campeau, I. W. Davies, Science 2017, 356, 426–430;
- 1cJ. B. Pyser, S. Chakrabarty, E. O. Romero, A. R. H. Narayan, ACS Cent. Sci. 2021, 7, 1105–1116.
- 2
- 2aI. A. H. Ahmad, G. L. Losacco, V. Shchurik, X. Wang, R. D. Cohen, A. N. Herron, S. Aiken, D. Fiorito, H. Wang, M. Reibarkh, T. Nowak, A. A. Makarov, D. R. Stoll, D. Guillarme, I. Mangion, V. K. Aggarwal, J.-Q. Yu, E. L. Regalado, Angew. Chem. Int. Ed. 2022, 61, e202117655;
- 2bA. Buitrago Santanilla, E. L. Regalado, T. Pereira, M. Shevlin, K. Bateman, L.-C. Campeau, J. Schneeweis, S. Berritt, Z.-C. Shi, P. Nantermet, Y. Liu, R. Helmy, C. J. Welch, P. Vachal, I. W. Davies, T. Cernak, S. D. Dreher, Science 2015, 347, 49–53;
- 2cN. Abdulhussain, S. Nawada, P. Schoenmakers, Chem. Rev. 2021, 121, 12016–12034;
- 2dD. A. Holland-Moritz, M. K. Wismer, B. F. Mann, I. Farasat, P. Devine, E. D. Guetschow, I. Mangion, C. J. Welch, J. C. Moore, S. Sun, R. T. Kennedy, Angew. Chem. Int. Ed. 2020, 59, 4470–4477;
- 2eJ. Cheon, J. Qin, L. P. Lee, H. Lee, Acc. Chem. Res. 2022, 55, 121–122;
- 2fJ. A. McIntosh, Z. Liu, B. M. Andresen, N. S. Marzijarani, J. C. Moore, N. M. Marshall, M. Borra-Garske, J. V. Obligacion, P. S. Fier, F. Peng, J. H. Forstater, M. S. Winston, C. An, W. Chang, J. Lim, M. A. Huffman, S. P. Miller, F.-R. Tsay, M. D. Altman, C. A. Lesburg, D. Steinhuebel, B. W. Trotter, J. N. Cumming, A. Northrup, X. Bu, B. F. Mann, M. Biba, K. Hiraga, G. S. Murphy, J. N. Kolev, A. Makarewicz, W. Pan, I. Farasat, R. S. Bade, K. Stone, D. Duan, O. Alvizo, D. Adpressa, E. Guetschow, E. Hoyt, E. L. Regalado, S. Castro, N. Rivera, J. P. Smith, F. Wang, A. Crespo, D. Verma, S. Axnanda, Z. E. X. Dance, P. N. Devine, D. Tschaen, K. A. Canada, P. G. Bulger, B. D. Sherry, M. D. Truppo, R. T. Ruck, L.-C. Campeau, D. J. Bennett, G. R. Humphrey, K. R. Campos, M. L. Maddess, Nature 2022, 603, 439–444;
- 2gY. Liu, J. Saurí, E. Mevers, M. W. Peczuh, H. Hiemstra, J. Clardy, G. E. Martin, R. T. Williamson, Science 2017, 356, eaam5349.
- 3
- 3aR. Bennett, R. D. Cohen, H. Wang, T. Pereira, M. A. Haverick, J. W. Loughney, D. C. Barbacci, P. Pristatsky, A. M. Bowman, G. L. Losacco, D. D. Richardson, I. Mangion, E. L. Regalado, Anal. Chem. 2022, 94, 1678–1685;
- 3bE. L. Regalado, I. A. Haidar Ahmad, R. Bennett, V. D'Atri, A. A. Makarov, G. R. Humphrey, I. Mangion, D. Guillarme, Acc. Chem. Res. 2019, 52, 1990–2002.
- 4
- 4aF. T. Mattrey, A. A. Makarov, E. L. Regalado, F. Bernardoni, M. Figus, M. B. Hicks, J. Zheng, L. Wang, W. Schafer, V. Antonucci, S. E. Hamilton, K. Zawatzky, C. J. Welch, TrAC Trends Anal. Chem. 2017, 95, 36–46;
- 4bK. Plachká, F. Švec, L. Nováková, Anal. Chim. Acta 2018, 1039, 149–161.
- 5
- 5aD. Lehnherr, Y.-h. Lam, M. C. Nicastri, J. Liu, J. A. Newman, E. L. Regalado, D. A. Di Rocco, T. Rovis, J. Am. Chem. Soc. 2020, 142, 468–478;
- 5bG. L. Losacco, H. Wang, I. A. Haidar Ahmad, J. DaSilva, A. A. Makarov, I. Mangion, F. Gasparrini, M. Lämmerhofer, D. W. Armstrong, E. L. Regalado, Anal. Chem. 2022, 94, 1804–1812.
- 6D. A. Strassfeld, R. F. Algera, Z. K. Wickens, E. N. Jacobsen, J. Am. Chem. Soc. 2021, 143, 9585–9594.
- 7
- 7aY. Wang, S. V. Olesik, Anal. Chem. 2019, 91, 935–942;
- 7bR. Bennett, S. V. Olesik, Anal. Chim. Acta 2018, 999, 161–168;
- 7cG. L. Losacco, S. Fekete, J.-L. Veuthey, D. Guillarme, Anal. Chim. Acta 2020, 1134, 84–95;
- 7dV. Desfontaine, G. L. Losacco, Y. Gagnebin, J. Pezzatti, W. P. Farrell, V. González-Ruiz, S. Rudaz, J.-L. Veuthey, D. Guillarme, J. Chromatogr. A 2018, 1562, 96–107;
- 7eG. L. Losacco, J. O. DaSilva, J. Liu, E. L. Regalado, J.-L. Veuthey, D. Guillarme, J. Chromatogr. A 2021, 1642, 462048;
- 7fJ. Molineau, Y. Hamel, M. Hideux, P. Hennig, S. Bertin, F. Mauge, E. Lesellier, C. West, J. Chromatogr. A 2021, 1658, 462631;
- 7gV. Pauk, M. Krejčí, K. Lemr, Anal. Chim. Acta 2021, 1157, 338401;
- 7hR. Bennett, M. Biba, J. Liu, I. A. Haidar Ahmad, M. B. Hicks, E. L. Regalado, J. Chromatogr. A 2019, 1595, 190–198;
- 7iT. L. Chester, J. D. Pinkston, Anal. Chem. 2004, 76, 4606–4613.
- 8
- 8aJ. O. DaSilva, D. Lehnherr, J. Liu, R. Bennett, I. A. Haidar Ahmad, M. Hicks, B. F. Mann, D. A. Di Rocco, E. L. Regalado, ACS Sustainable Chem. Eng. 2020, 8, 6011–6021;
- 8bJ. Liu, A. A. Makarov, R. Bennett, I. A. Haidar Ahmad, J. DaSilva, I. Mangion, B. F. Mann, E. L. Regalado, Anal. Chem. 2019, 91, 13907–13915;
- 8cM. Lísa, M. Holčapek, Anal. Chem. 2015, 87, 7187–7195;
- 8dK. Plachká, T. Gazárková, J. Škop, D. Guillarme, F. Svec, L. Nováková, Anal. Chem. 2022, 94, 4841–4849.
- 9
- 9aC. West, TrAC Trends Anal. Chem. 2019, 120, 115648;
- 9bD. Roy, A. Tarafder, L. Miller, TrAC Trends Anal. Chem. 2021, 145, 116464;
- 9cG. L. Losacco, J.-L. Veuthey, D. Guillarme, TrAC Trends Anal. Chem. 2021, 141, 116304;
- 9dD. Roy, M. Farooq Wahab, T. A. Berger, D. W. Armstrong, Anal. Chem. 2019, 91, 14672–14680;
- 9eL. Khvalbota, D. Roy, M. Farooq Wahab, S. K. Firooz, A. Machyňáková, I. Špánik, D. W. Armstrong, Anal. Chim. Acta 2020, 1120, 75–84.
- 10Y. Dong, A. W. Schuppe, B. K. Mai, P. Liu, S. L. Buchwald, J. Am. Chem. Soc. 2022, 144, 5985–5995.
- 11E. L. Regalado, C. J. Welch, TrAC Trends Anal. Chem. 2015, 67, 74–81.