Fast Liquid Chromatography for Real-Time Process Monitoring of Chemical Reactions in Batch and Flow
Year: 2026
Type: preprint
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.
Source: ChemRxiv
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223061967