engleski

Monitoring of entacapone synthesis reaction by "in-line" Raman spectroscopy and multivariate analysis

In recent years, it has become obvious that the production of drugs will have to deal with new challenges including the control of parameters defining the quality of particles during the processes of preparation and isolation of the active substances. The standard monitoring procedures usually include analytical measurements with samples taken out of the chemical reactor and do not provide a real-time information on chemical reactions. Hence, new methodologies are crucial for a better quality control and higher product efficiency. These should enable a non-invasive detection of different physical and chemical transformations of the reactants and products during the manufacturing process. Here we report on using in-line Raman spectroscopy for monitoring Knoevenagel condensation reaction being the final step in preparation of drug entacapone. Entacapone, 2-cyano-N, N-diethyl-3-(3, 4-dihydroxy-5-nitrophenyl) propenamide is a selective inhibitor of catechol-O-methyltransferase, an enzyme responsible for the metabolism of L-dopa being a precursor to dopamine. It is clinically used and prescribed for the treatment of Parkinson’s diseaseRaman spectroscopy can be used for the remote detection through fiber optics facilitating the in-line monitoring of chemical reactions and generating data in real time. The combined application of in-line Raman spectroscopy and multivariate analysis for the real time monitoring of entacapone synthesis will be reported and discussed.

entacapone; synthesis; "in-line" Raman spectroscopy; multivariate analysis; chromatography

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