Rapid Monitoring of Chemical Reactions Made Possible by Ultrahigh-Performance Liquid Chromatography

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Matthias Pursch has presented a method for monitoring small molecule and polymer reactions in real time using fast online ultrahigh-performance liquid chromatography (UHPLC) as part of his keynote lecture at HPLC 2023 (1). He demonstrated that when coupled with size-exclusion chromatography (SEC), UHPLC enables rapid analysis with cycle times as low as 1.5 min, providing quantitative results and insights into the reaction process. The methodology was successfully applied to various chemical reactions, including hydrolysis, derivatization, isocyanate reactions, and polymer degradation kinetics. This advancement in online LC technology has the potential to revolutionize process monitoring in diverse industries.

In his talk, Pursch addressed the need for efficient analytical tools to determine reaction speed and identify end products in chemical processes. While online gas chromatography (GC) and spectroscopy techniques have been widely adopted for reaction monitoring, online LC has been limited due to its inherent difficulty, lack of robustness, and slow analysis speed. However, the advent of UHPLC, along with advancements in column technology and instrument features, has significantly improved the speed and reliability of LC instrumentation.

Pursch and his team employed both UHPLC and SEC to monitor a range of chemical reactions. By utilizing a short sub-2-μm silica particle column, they achieved fast separations in less than 1 min. The entire LC cycle, including separation and sampling, could be completed in as little as 1.5 min, allowing for real-time monitoring of chemical reactions. The resulting data were displayed in run charts, providing quantitative information in a timely manner.


The method was successfully applied to different areas of research. The team investigated the temperature- and pH-dependent hydrolysis of a vinyl ester acid, enabling the monitoring of reactions as fast as 10 min using UHPLC. They also studied the speed of aldehyde derivatization in polyethylene glycols using 2,4-dinitrophenylhydrazine (DNPH), revealing a dependence on the PEG type and molecular weight. In addition, the reaction of isocyanates with short alkyl chain alcohols was examined, allowing for the observation of both starting compounds, intermediates, and reaction products. Finally, the researchers explored polymer biodegradation kinetics, specifically dextrans, using fast sampling and SEC with online multi-angle light scattering (SEC-MALS).


(1) Pursh, M. Rapid Monitoring of Small Molecule and Polymer Reactions by Online UHPLC. Presented at: HPLC 2023. June 18–22, 2023. Duesseldorf, Germany. KN08.