Fast Liquid Chromatography for Real-Time Process Monitoring of Chemical Reactions in Batch and Flow
5 affiliations
- 1Department of Chemistry
- 2University of Michigan
- 3Process Research and Development
- 4AbbVie Inc.
- 5University of British Columbia
Abstract
Process analytical technologies (PATs) are increasingly vital tools in process research and development, enabling realtime monitoring of a reaction’s chemical and physical parameters. Although numerous commercial PATs exist, many are limited by sampling frequency, material consumption, or requiring unique chemical labels for spectroscopic analysis. Herein, we report a rapid, label-free analytical sampling platform that integrates fast high-pressure liquid chromatography (HPLC) with electrospray ionizationmass spectrometry (ESI-MS) for the direct, real-time monitoring of chemical reactions. Reactions are pumped into a four-port nanovolume injection valve and are injected onto short LC columns at high mobile phase flow rates, which enables chromatographic separations on the time-scale of 6–20 seconds. We demonstrate the utility of this technology by monitoring two rapid reactions relevant to the pharmaceutical industry: a photocatalytic thiol–ene reaction and a metallaphotoredox aryl sulfonamidation reaction. In each case, data-rich reaction progress profiles are obtained for monitoring the reaction progress in real-time, demonstrating the platform’s capability to deliver detailed reaction insights with minimal sample consumed (4 nL injection-1). Its modular design is adaptable to different reactor geometries and scales, while maintaining device simplicity to enable straightforward integration into existing workflows in industrial settings.
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BibTeX
@misc{snyder2026fast,
title = {{Fast Liquid Chromatography for Real-Time Process Monitoring of Chemical Reactions in Batch and Flow}},
author = {Ryan T. Snyder and Trevor J. Kempen and Yue Xin and Juan Vazquez-Lopez and G. Thomas Knecht and Kaid C. Harper and Westin H. Morrill and Bradley A. Greiner and Nicholas G. W. Cowper and Anna V. Bay and Kyle T. Jaunich and Corey R. J. Stephenson and Robert T. Kennedy},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010688/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010688/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Fast Liquid Chromatography for Real-Time Process Monitoring of Chemical Reactions in Batch and Flow
AU - Ryan T. Snyder
AU - Trevor J. Kempen
AU - Yue Xin
AU - Juan Vazquez-Lopez
AU - G. Thomas Knecht
AU - Kaid C. Harper
AU - Westin H. Morrill
AU - Bradley A. Greiner
AU - Nicholas G. W. Cowper
AU - Anna V. Bay
AU - Kyle T. Jaunich
AU - Corey R. J. Stephenson
AU - Robert T. Kennedy
PY - 2026
DA - 2026/10/20
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010688/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010688/v1
AB - Process analytical technologies (PATs) are increasingly vital tools in process research and development, enabling realtime monitoring of a reaction’s chemical and physical parameters. Although numerous commercial PATs exist, many are limited by sampling frequency, material consumption, or requiring unique chemical labels for spectroscopic analysis. Herein, we report a rapid, label-free analytical sampling platform that integrates fast high-pressure liquid chromatography (HPLC) with electrospray ionizationmass spectrometry (ESI-MS) for the direct, real-time monitoring of chemical reactions. Reactions are pumped into a four-port nanovolume injection valve and are injected onto short LC columns at high mobile phase flow rates, which enables chromatographic separations on the time-scale of 6–20 seconds. We demonstrate the utility of this technology by monitoring two rapid reactions relevant to the pharmaceutical industry: a photocatalytic thiol–ene reaction and a metallaphotoredox aryl sulfonamidation reaction. In each case, data-rich reaction progress profiles are obtained for monitoring the reaction progress in real-time, demonstrating the platform’s capability to deliver detailed reaction insights with minimal sample consumed (4 nL injection-1). Its modular design is adaptable to different reactor geometries and scales, while maintaining device simplicity to enable straightforward integration into existing workflows in industrial settings.
ER -