Monitoring and Quantification of Omeprazole Synthesis Reaction by In-Line Raman Spectroscopy and Characterization of the Reaction Components

Abstract

The development of a quantitative in-line Raman spectroscopic method for the monitoring of the active pharmaceutical ingredient, omeprazole synthesis reaction, and characterization of the reaction components is described. In-line monitoring was performed both with Fourier transform and dispersive Raman spectrometers. Prior to reaction monitoring, the reaction components were characterized off-line by means of Raman and NMR spectroscopy, both in solution and in solid state. To unequivocally confirm the presence of each component in the reaction mixture, a state of the art LC-SPE/NMR methodology was also used. Owing to its higher sensitivity, dispersive Raman spectroscopy was further employed for quantification purposes. The spectroscopic measurements and the complementary HPLC analyses, used in the calibration development, were gathered from a set of experiments, performed at a 1 L scale. On the basis of the data set obtained from the calibration experiments, a predictive partial least-squares (PLS) regression model was developed for all three reaction components, enabling an accurate determination of the percentage of each component present in the reaction mixture, at any time after the point when 25% of the starting material has been consumed. The model was successfully used to monitor the reaction progress in a kilo-lab scale experiment and can further be used as a fast response analytical tool in process optimization. It also has the potential to be used as part of a feedback control loop in the production plant.

Qualitative and quantitative analysis of therapeutic solutions using Raman and infrared spectroscopy

“…IR and Raman spectroscopy are powerful analytical tools widely used for characterisation of organic molecules such as, for example, therapeutic drugs [20]. Although primarily used in industry and research laboratories as screening tools to monitor whether a synthesis process has been successful [21], coupling the molecular specificity of the spectra collected with optimised quantitative approaches strongly promotes the techniques for therapeutic solution screening in the clinical environment [22]. In previous studies, although encouraging results are documented for monitoring a number of molecules such as ganciclovir [23] or 5FU [24], directly in the infusion bag, the material used for the packaging, often polystyrene like, also has strong contributions to the spectra that can limit the usable analytical range and lead to difficulties in quantifying and/or identifying the chemotherapeutic drugs accurately [25].…”

Application of Raman Spectroscopy for In-Line Measurement of Dispersion Uniformity of Polypropylene–Polystyrene Blends During Melt Extrusion

“…Raman spectroscopy, which is based on inelastic light scattering, has many well-resolved spectral features, providing the basis for quantitative analysis and good specificity for qualitative analysis. 4 In addition, owing to its powerful capability of providing rich information on molecular structure and chemical composition without destruction and preparation of the sample, in-line Raman spectroscopy has been adopted to obtain real-time information in a number of industries such as pharmaceutical, [5][6][7] bioengineering, 8,9 and chemical. 10,11 In polymer fields, the Raman spectroscopy technique has been reported for on-line measurement of crystallinity, [12][13][14] for monitoring polymerization reactions, 15,16 for on-line measurement of polyethylene pellet density, 17 etc.…”

In situ and operando Raman spectroscopy of semiconducting photoelectrodes and devices for photoelectrochemistry

“…Finally, a separate discussion must be conducted for the qualitative and quantitative analysis of liquid reaction products using RS. In the literature, many excellent examples are reported on chemical analysis of liquid reaction environments performed using RS [39,[71][72][73][74][75]. These studies predominantly deal with relatively concentrated solutions and products, with concentrations up to hundreds of mmoles l −1 [39].…”