Capillary Electrophoresis in Drug Stereoisomer Analysis

Gerhard Scriba, Pharmaceutical/Medicinal Chemistry, Friedrich Schiller University, Jena, Germany (gerhard.scriba@uni-jena.de)

The importance of the stereochemistry of pharmaceutical drugs is well recognized because stereoisomers often differ in their pharmacological, toxicological and/or pharmacokinetic profiles. As a consequence, the majority of small molecule drugs of the top 10 products according to their worldwide sales in 2016 are single enantiomer drugs [1]. Consequently, for drug development and quality control, the determination of the stereoisomeric composition and purity of a compound requires sensitive and accurate analytical methods in order to determine the stereoisomer ratios in synthetic products, pharmaceutical formulations and biological samples. Besides HPLC, capillary electrophoresis (CE) has become an attractive alternative for this purpose.

In CE, the chiral selector is added to the background electrolyte acting as a pseudostationary phase, which is also mobile in contrast to chromatographic methods. Consequently, two stereoselective principles contribute to stereoisomer separations: (1) the formation of transient diastereomeric complexes between analyte enantiomers and the chiral selector (also referred to as the thermodynamic or chromatographic enantioselective mechanism) and (2) the mobility of the complexes (electrophoretic enantioselective mechanism). Both principles can cooperate or counteract each other.

The current presentation will discuss recent applications of chiral CE methods for the determination of the enantiomeric purity of pharmaceutical drugs including the effects of analyte complexation and mobility of the selector-analyte complexes on the enantioseparation. Precise and accurate methods were developed using a quality by design (QbD) approach and design of experiment (DoE) methodologies and eventually applied to the analysis of bulk drug or pharmaceutical formulations.

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Abstract Reference & Short Personal Biography of Presenting Author

[1] G. Sedelmeier, J. Sedelmeier, Chimia 71 (2017) 730.

Gerhard K. E. Scriba is a full professor at the Department of Medicinal/Pharmaceutical Chemistry at the Friedrich Schiller University Jena, Germany. He studied Pharmacy at the University of Bonn and received his Ph.D. in 1984 from the University of Münster. Between 1986 and 1988 he worked as a post-doc at the Department of Pharmaceutical Chemistry of the University of Kansas, Lawrence, Kansas, USA before returning to the University of Münster where he finished his habilitation in 1995. Since 1999 he holds his current position at the University of Jena where he served as head of the School of Pharmacy from 2005 to 2013 and as Dean of Study Affairs of the Faculty of Biological Sciences from 2010 to 2013. He received the Rottendorf-Prize for Pharmaceutical Sciences in 1995 and the Johann-Wolfgang-Döbereiner-Prize of the German Pharmaceutical Association in 1997.

Prof. Scriba has published over 175 research and review papers and more than 20 book chapters. He is editor of the book Chiral Separations (2^nd and 3^rd edition) and co-editor of the journal Chromatographia. Furthermore, he is and a member of the editorial boards of the journals Electrophoresis, Journal of Separation Science and Journal of Pharmaceutical and Biomedical Analysis and regularly serves as guest editor of the paper symposia "Pharmaceutical Analysis" of Electrophoresis. Prof. Scriba is a member of the working group Pharmaceutical Chemistry of the German Pharmacopoeia, the scientific commission of the German Drug Codex (DAC) and an advisor for the World Health Organization (WHO) on quality control and pharmacopoeial specifications for medicines. Between 2007 and 2016 he served as a member of the scientific advisory board of the German Federal Institute for Drugs and Medical Devices (BfArM).

The research focuses on the analysis of drugs and peptides including stereoisomer analysis by capillary electrophoresis and HPLC as well as mechanistic studies on the interaction between selectors and solutes. A further research topic covers capillary electrophoresis-based enzyme assays.