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SPECTROSCOPY


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Enantioselective Raman Spectroscopy – A new tool for process monitoring in the pharmaceutical industry?


Johannes Kiefer


Technische Thermodynamik, Universität Bremen Badgasteiner Str. 1, 28359 Bremen, Germany


Introduction


Many pharmaceutically active molecules are chiral and their physiological effects are determined by enantioselective interactions with proteins in a biological organism. These effects can be very different for the enantiomers of a chiral substance. Hence, it is of utmost importance to produce enantiopure substances in the pharmaceutical industry.


The prerequisite for optimizing the production of enantiopure substances is the development and implementation of suitable analytical techniques for process monitoring. However, a major problem in this context is that the enantiomers are virtually identical in terms of molecular structure. This implies that they also exhibit identical physicochemical properties, which makes it very difficult to distinguish between them. In particular, methods that provide structural information and allow for enantioselective discrimination are rare. The list of available methods includes microwave and fluorescence spectroscopy, nuclear magnetic resonance (NMR), vibrational circular dichroism (VCD), Raman optical activity (ROA), cavity ringdown polarimetry, and surface enhanced Raman spectroscopy (SERS). However, all these methods have their particular disadvantages. Some require sampling and sample preparation, some require long measurement times, and some require adding tracers or nanoparticles. Therefore, the suitability of these methods for process monitoring in situ and in real time is limited. Hence, there is a need for new Process Analytical Technology (PAT) to enable inline measurements with high temporal resolution, good reproducibility, and high accuracy as well as precision.


Enantioselective Raman Spectroscopy


Although being a standard tool in many analytical labs, conventional Raman spectroscopy has not been considered as


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