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» SPECTROSCOPY


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.





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Another key feature in the context of process monitoring is the short acquisition time required to record an esR spectrum. If required, this measurement time can be on the order of nanoseconds and repetition rates up to kHz are basically possible. This is a major advantage over many other existing analytical methods for enantioselective measurements. Consequently, the new esR method will be a useful technology for both real-time process monitoring and fast screening of chiral samples.


A few challenges remain regarding the experimental realization and the data evaluation. First experiments have, on the one hand, demonstrated that the method works, but, on the other hand, they also revealed the need for high-quality achromatic half-wave plates. Otherwise, artifacts appear in the signal and must be taken into account in the data processing and evaluation. However, these challenges will certainly not prevent the method to be deployed in production processes in the future.


Conclusion


In conclusion, the question in the title can without a doubt be answered with “yes”. The recently developed enantioselective Raman spectroscopy approach can provide qualitative and quantitative measurements with high accuracy, short measurement times, and high repetition rates. Therefore, it is a very promising candidate for inline process monitoring in the pharmaceutical industry.


Acknowledgement The author thanks Dr. Kristina Noack for helpful discussions.


Figure 1. Schematic experimental esR spectroscopy setup: L = lens, BD = beam dump, HWP = half-wave plate, PBS = polarizing beam splitter, SM1/SM2 = spectrometer. The polarization diagrams to the left indicate how the half-wave plate breaks the symmetry to enable enantioselective detection of the D- and L- enantiomer of a chiral substance.


doing both a qualitative and quantitative measurement. This makes it a perfect tool for process analytical technology. A question that may arise, however, is whether or not the quantitative analysis can yield information about the ratio of the enantiomers in a mixture. Such capability would mean that the technique can be used to monitor the enantiomeric purifi cation in a production process. The answer to this question is: yes, it can! Theoretical considerations have demonstrated that a careful and thoughtful alignment of the half-wave plate in the setup facilitates the determination of the overall concentration of the chiral substance and, in addition, the enantiomeric ratio.2


54 | | May/June 2016 Author Biography


Prof. Dr. Johannes Kiefer is Chair Professor and Head of the division Technische Thermodynamik at the University of Bremen, Germany. In addition, he is an Honorary Professor at the University of Aberdeen, Scotland, and he holds a guest professorship of the Erlangen Graduate School in Advanced Optical Technologies (SAOT) at the University Erlangen-Nuremberg, Germany. His research interests are the areas of developing and applying spectroscopic techniques for the characterization of advanced materials and processes.


References 1.


2.


Kiefer J, Noack K. Universal enantioselective discrimination by Raman spectroscopy. Analyst 2015;140(6):1787-1790.


Kiefer, J. Quantitative enantioselective Raman spectroscopy. Analyst 2015;140(15): 5012-5018.





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