Deep UV resonance Raman detection in a liquid core waveguide for online identification and quantification in column liquid chromatography

This study presents a novel experimental setup that couples high-performance liquid chromatography (HPLC) with a custom-built deep ultraviolet resonance Raman spectrometer (DUV-RRS) for the identification and quantification of analytes following chromatographic separation. For the first time, a liquid-core waveguide (LCW) was integrated into an HPLC-DUV-RRS system to enhance Raman signal intensity. A cost- efficient and eco-friendly deep UV pulsed laser was employed to achieve this advancement with an average output power of only 0.5 mW. The combination of LCW and DUV-RRS enables strong absorption of the excitation light by the target molecules due to the extended optical pathlength within the LCW. The system's performance was evaluated using two pharmaceutical agents, metformin and naproxen. The detector's sensitivity was found to be compound-dependent. For metformin and naproxen, detection limits of 0.07 μg and 0.20 μg, respectively, were achieved on-column, representing a 3.5-fold and 1.2-fold improvement over previous setups without LCW integration, even though the exposure time of the Raman detector was reduced by a factor of up to 60. While metformin showed a linear correlation between Raman signal intensity and concentration at lower concentrations, no linear relationship could be observed for naproxen due to absorption effects. Nevertheless, partial least squares (PLS) analysis revealed a linear relationship between signal intensity and analyte concentration for both substances across the full tested concentration range. These findings demonstrate the potential of LCW-enhanced DUV-RRS as a sensitive and selective detection method in hyphenated analytical systems, particularly for analytes with favorable resonance Raman properties. • Deep UV resonance Raman detector for HPLC. • Liquid core waveguide. • Low laser power.