(470a) Preparation of Monolithic Materials for Continuous Annular Electro-Chromatographic Separations of Active Pharmaceutical Ingredients

Capillary electrochromatography (CEC) is a very powerful tool for analytical separations of, e.g., active pharmaceutical ingredients. While its high separation efficiency (over 500000 plates per meter [1]) is unmatched, its low throughputs (only several nanolitres per minute) rend it irrational for preparative use. As downstream processing of high value added products becomes more and more a relevant cost factor [2], the need arises to increase the throughput of chromatographic applications while maintaining the high separation efficiency. An attempt in this field is the development of a continuous annular electro-chromatography (CAEC) process that combines the electro-chromatographic principle with a continuous mode of operation [3,4]. The CAEC prototype includes an immobile annular bed inside a 300 µm gap formed by two concentric glass cylinders with rotating feed and sampling lines. An online detection system enables advanced automation and quality control, so that the process accords to the PAT (Process Analytical Technology) guidelines specified by the FDA. We present the development of different monolithic stationary phases for this CAEC prototype. Silica based monoliths with a wide variety of different chemical functionalities were prepared via a sol-gel process following procedures published by Ding et al.[5] and Yan et al.[6]. One step approaches as well as two step methods where the chemical functionality was introduced in a subsequent step were pursued. Shrinking, a common problem in the preparation of monolithic materials was drastically reduced when silica particles (10 µm) were added during the sol-gel process. Apart from silica based materials also organic polymers were investigated following a procedure published by Schmid et al. [7]. The monoliths were implemented in capillaries for CEC (100 µm i.d.) as well as in a planar prototype system. This planar system represents a fraction of the annular prototype and already allows continuous preparative electro-chromatography. Additionally, the prepared materials were examined using SEM, nitrogen adsorption, FTIR, Raman-spectroscopy and DSC.

This work is supported by the 7th Research Framework Programme of the European Commission (Grant agreement number: NMP2-SL-2008-206707).

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