M E T H O D S I N M O L E C U L A R B I O L O G Y ™

Series EditorJohn M. Walker

School of Life SciencesUniversity of Hertfordshire

Hat fi eld, Hertfordshire, AL10 9AB, UK

For further volumes:http://www.springer.com/series/7651

Chiral Separations

Methods and Protocols

Second Edition

Edited by

Gerhard K.E. Scriba

Department of Pharmaceutical Chemistry, Friedrich Schiller University Jena, Jena, Germany

EditorGerhard K.E. ScribaDepartment of Pharmaceutical ChemistryFriedrich Schiller University JenaJena, Germany

ISSN 1064-3745 ISSN 1940-6029 (electronic)ISBN 978-1-62703-262-9 ISBN 978-1-62703-263-6 (eBook)DOI 10.1007/978-1-62703-263-6Springer New York Heidelberg Dordrecht London

Library of Congress Control Number: 2012952732

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Dedication

To Beate, Sabrina, and Rebecca

vii

What can more resemble my hand or my ear, and be more equal in all points, than its image in a mirror? And yet, I cannot put such a hand as is seen in the mirror in the place of its original.

Immanuel Kant Prolegomena to Any Future Metaphysics That Will Be Able to Come Forward as Science (1783)

ix

Preface

The importance of the stereochemistry of compounds is well recognized in chemistry and life sciences since Louis Pasteur discovered the phenomenon of chirality in 1848. The enantiomers of chiral compounds often differ in their biological, pharmacological, toxico-logical, and/or pharmacokinetic pro fi le. This has become evident speci fi cally in pharma-ceutical sciences, but it also affects chemistry, biology, food chemistry, forensics, etc., and is re fl ected in the requirements for chiral compounds by regulatory authorities worldwide. For example, the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) require the development of a single enantiomer of a drug candidate if the enantiomers differ in their pharmacological action, toxicological pro fi le, etc. As a conse-quence, seven drugs of the top ten drugs (not counting biotechnological drugs) according to their sales in the USA in 2010 ( www.drugs.com/top200.html , accessed February 21, 2012) are single enantiomer drugs, while two drugs are achiral compounds. One product is a combination of a chiral and a racemic drug. In fact, the top three products are single enantiomer drugs. However, the importance of chirality does not stop here but is impor-tant to any research in life sciences.

Generally, there is a great demand for analytical methods that are able to discriminate between enantiomers in order to analyze the enantiomeric purity of compounds from natu-ral or chemical sources not only in pharmaceutical sciences but in any fi eld of bioactive compounds including chemistry, biology, biochemistry, forensic and environmental sci-ences, and many others. Chromatographic techniques dominated the fi eld of enantiosepa-rations early on, but electrophoretic methods have gained increasing importance in recent years. While some compounds may be analyzed only with one technique based on their physicochemical properties, often the analyst can chose between two or more analytical techniques for a given analyte. This requires knowledge of the strengths and weaknesses of each technique in order to select the most appropriate method for the given problem.

The focus of Chiral Separations: Methods and Protocols, 2nd edition is clearly on analyti-cal separation sciences by chromatographic and electrophoretic techniques although simu-lated moving bed chromatography has also been included, which is primarily used as a preparative method. The book does not claim to comprehensively cover each possible chiral separation mechanism but to give an overview and especially practically oriented applica-tions of the most important analytical techniques in chiral separation sciences. Thus, the book follows the well-established scheme of the Methods and Protocols series. Some review chapters give an overview of the current state of art in the respective fi eld. However, most chapters are devoted to the description of the typical analytical procedures providing reli-able and established procedures for the user. Critical points are highlighted so that the user is enabled to transfer the described method to his/her actual separation problem.

Sixty-four authors from 34 research laboratories in 17 countries have contributed by sharing their insight and expert knowledge of the techniques. I would like to take the opportunity to thank all authors for their efforts and valuable contributions.

x Preface

Chiral Separations: Methods and Protocols, 2nd edition should be helpful for analytical chemists working on stereochemical problems in fi elds of pharmacy, chemistry, biochemis-try, food chemistry, molecular biology, forensics, environmental sciences, or cosmetics in academia, government, or industry.

Jena, Germany Gerhard K.E. Scriba

xi

Contents

Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ixContributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xv

1 Chiral Recognition in Separation Science: An Overview. . . . . . . . . . . . . . . . . . 1Gerhard K.E. Scriba

2 Enantioseparations by Thin-Layer Chromatography . . . . . . . . . . . . . . . . . . . . 29Massimo Del Bubba, Leonardo Checchini, Alessandra Cincinelli, and Luciano Lepri

3 Gas-Chromatographic Enantioseparation of Unfunctionalized Chiral Hydrocarbons: An Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45Volker Schurig and Diana Kreidler

4 HPLC Enantioseparation on Cyclodextrin-Based Chiral Stationary Phases. . . . 69Yong Wang and Siu Choon Ng

5 Enantioseparations by High-Performance Liquid Chromatography Using Polysaccharide-Based Chiral Stationary Phases: An Overview. . . . . . . . . 81Bezhan Chankvetadze

6 Common Screening Approaches for Efficient Analytical Method Development in LC and SFC on Columns Packed with Immobilized Polysaccharide-Derived Chiral Stationary Phases . . . . . . . . . . . . . . . . . . . . . . . 113Pilar Franco and Tong Zhang

7 Chiral Separations by HPLC on Immobilized Polysaccharide Chiral Stationary Phases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 127Imran Ali, Zeid A. AL-Othman, and Hassan Y. Aboul-Enein

8 Enantioseparations by High-Performance Liquid Chromatography Using Macrocyclic Glycopeptide-Based Chiral Stationary Phases: An Overview. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137István Ilisz, Anita Aranyi, Zoltán Pataj, and Antal Péter

9 Enantioseparations of Primary Amino Compounds by High-Performance Liquid Chromatography Using Chiral Crown Ether-Based Chiral Stationary Phase . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 165Myung Ho Hyun

10 Screening of Pirkle-Type Chiral Stationary Phases for HPLC Enantioseparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 177Gregory K. Webster and Ted J. Szczerba

11 Enantioseparations by High-Performance Liquid Chromatography Based on Chiral Ligand-Exchange. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191Benedetto Natalini, Roccaldo Sardella, and Federica Ianni

xii Contents

12 Enantioseparations by High-Performance Liquid Chromatography Using Molecularly Imprinted Polymers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 209David A. Spivak

13 Chiral Mobile Phase Additives in HPLC Enantioseparations . . . . . . . . . . . . . . 221Lushan Yu, Shengjia Wang, and Su Zeng

14 Chiral Benzofurazan-Derived Derivatization Reagents for Indirect Enantioseparations by HPLC . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 233Toshimasa Toyo’oka

15 Separation of Racemic 1-(9-Anthryl)-2,2,2-trifluoroethanol by Sub-/Supercritical Fluid Chromatography . . . . . . . . . . . . . . . . . . . . . . . . . 249Xiqin Yang, Leo Hsu, and Gerald Terfloth

16 Chiral Separations by Simulated Moving Bed Method Using Polysaccharide-Based Chiral Stationary Phases. . . . . . . . . . . . . . . . . . . . . . . . . 257Toshiharu Minoda

17 Enantioseparations by Capillary Electrophoresis Using Cyclodextrins as Chiral Selectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271Gerhard K.E. Scriba and Pavel Jáč

18 Application of Dual Cyclodextrin Systems in Capillary Electrophoresis Enantioseparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289Anne-Catherine Servais and Marianne Fillet

19 Enantioseparations in Nonaqueous Capillary Electrophoresis Using Charged Cyclodextrins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297Anne-Catherine Servais and Marianne Fillet

20 Use of Macrocyclic Antibiotics as the Chiral Selectors in Capillary Electrophoresis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307Chengke Li and Jingwu Kang

21 Application of Polymeric Surfactants in Chiral Micellar Electrokinetic Chromatography (CMEKC) and CMEKC Coupled to Mass Spectrometry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319Jun He and Shahab A. Shamsi

22 Cyclodextrin-modified Micellar Electrokinetic Chromatography for Enantioseparations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349Wan Aini Wan Ibrahim, Dadan Hermawan, and Mohd Marsin Sanagi

23 Cyclodextrin-Mediated Enantioseparation in Microemulsion Electrokinetic Chromatography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363Claudia Borst and Ulrike Holzgrabe

24 Chiral Separations by Capillary Electrophoresis Using Proteins as Chiral Selectors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377Jun Haginaka

25 Enantioseparation by Chiral Ligand-Exchange Capillary Electrophoresis . . . . . 393Yi Chen and Lijuan Song

26 Experimental Design Methodologies in the Optimization of Chiral CE or CEC Separations: An Overview . . . . . . . . . . . . . . . . . . . . . . . 409Bieke Dejaegher, Debby Mangelings, and Yvan Vander Heyden

xiiiContents

27 Chiral Capillary Electrophoresis–Mass Spectrometry . . . . . . . . . . . . . . . . . . . . 429Elena Domínguez-Vega, Antonio L. Crego, and Maria Luisa Marina

28 Application of Chiral Ligand-Exchange Stationary Phases in Capillary Electrochromatography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 443Martin G. Schmid

29 Polysaccharide-Derived Chiral Stationary Phases in Capillary Electrochromatography Enantioseparations. . . . . . . . . . . . . . . . . . . . . . . . . . . 457Zhenbin Zhang, Hanfa Zou, and Junjie Ou

30 Open Tubular Molecular Imprinted Phases in Chiral Capillary Electrochromatography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 469Won Jo Cheong and Song Hee Yang

31 Enantioseparations in Capillary Electrochromatography Using Sulfated Poly β-Cyclodextrin-Modified Silica-Based Monolith as Stationary Phase. . . . . 489Ruijuan Yuan and Guosheng Ding

32 Cyclodextrin-Mediated Enantioseparations by Capillary Electrochromatography. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505Dorothee Wistuba and Volker Schurig

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 525

xv

Contributors

HASSAN Y. ABOUL-ENEIN • National Pharmaceutical and Medicinal Chemistry Department , Research Centre , Cairo , Egypt

IMRAN ALI • Department of Chemistry , Jamia Millia Islamia (Central University) , New Delhi , India

ZEID A. AL-OTHMAN • Department of Chemistry , King Saud University , Riyadh , Kingdom of Saudi Arabia

ANITA ARANYI • Department of Inorganic and Analytical Chemistry , University of Szeged , Szeged , Hungary

CLAUDIA BORST • Institute of Pharmacy and Food Chemistry, University of Würzburg , Würzburg , Germany

MASSIMO DEL BUBBA • Department of Chemistry , University of Florence , Sesto Fiorentino , Italy

BEZHAN CHANKVETADZE • Institute of Physical and Analytical Chemistry, Tbilisi State University , Tbilisi , Georgia

LEONARDO CHECCHINI • Department of Chemistry , University of Florence , Sesto Fiorentino , Italy

YI CHEN • Key Laboratory of Analytical Chemistry for Living Biosystems , Chinese Academy of Sciences , Beijing , China

WON JO CHEONG • Department of Chemistry , Inha University , Incheon , South Korea ALESSANDRA CINCINELLI • Department of Chemistry , University of Florence ,

Sesto Fiorentino , Italy ANTONIO L. CREGO • Department of Analytical Chemistry , University of Alcalá ,

Alcalá de Henares , Spain BIEKE DEJAEGHER • Department of Analytical Chemistry and Pharmaceutical Technology ,

Vrije Universiteit Brussel , Brussels , Belgium GUOSHENG DING • Analysis Center, Tianjin University , Tianjin , China ELENA DOMÍNGUEZ-VEGA • Department of Analytical Chemistry , University of Alcalá ,

Alcalá de Henares , Spain MARIANNE FILLET • Department of Pharmaceutical Sciences , University of Liège , Liège ,

Belgium PILAR FRANCO • Chiral Technologies Europe , Illkirch , France JUN HAGINAKA • School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women’s

University , Nishinomiya , Japan JUN HE • Department of Chemistry , Center of Biotechnology and Drug Design,

Georgia State University , Atlanta , GA , USA DADAN HERMAWAN • Department of Chemistry , Universiti Teknologi Malaysia , Johor ,

Malaysia YVAN VANDER HEYDEN • Department of Analytical Chemistry and Pharmaceutical

Technology , Vrije Universiteit Brussel , Brussels , Belgium ULRIKE HOLZGRABE • Institute of Pharmacy and Food Chemistry, University of Würzburg ,

Würzburg , Germany

xvi Contributors

LEO HSU • GlaxoSmithKline Research and Development , King of Prussia , PA , USA MYUNG HO HYUN • Department of Chemistry and Chemistry , Pusan National University ,

Busan , South Korea FEDERICA IANNI • Dipartimento di Chimica e Tecnologia del Farmaco , Università degli

Studi di Perugia , Perugia , Italy WAN AINI WAN IBRAHIM • Separation Science and Technology Group (SepSTec) ,

Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia , Johor , Malaysia

ISTVÁN ILISZ • Department of Inorganic and Analytical Chemistry , University of Szeged , Szeged , Hungary

PAVEL JÁČ • Department of Pharmaceutical/Medicinal Chemistry , Friedrich Schiller University Jena , Jena , Germany

JINGWU KANG • Chinese Academy of Sciences, Shanghai Institute of Organic Chemistry , Shanghai , China

DIANA KREIDLER • Institute of Organic Chemistry, University of Tübingen , Tübingen , Germany

LUCIANO LEPRI • Department of Chemistry , University of Florence , Sesto Fiorentino , Italy CHENGKE LI • Chinese Academy of Sciences, Shanghai Institute of Organic Chemistry ,

Shanghai , China DEBBY MANGELINGS • Department of Analytical Chemistry and Pharmaceutical

Technology , Vrije Universiteit Brussel , Brussels , Belgium MARIA LUISA MARINA • Department of Analytical Chemistry , University of Alcalá , Alcalá

de Henares , Spain TOSHIHARU MINODA • Daicel Corporation , Niigata , Japan BENEDETTO NATALINI • Dipartimento di Chimica e Tecnologia del Farmaco , Università

degli Studi di Perugia , Perugia , Italy SIU CHOON NG • School of Chemical and Biomedical Engineering, Nanyang

Technological University , Singapore , Singapore JUNJIE OU • National Chromatographic R&A Center, Dalian Institute of Chemical

Physics , Dalian , China ZOLTÁN PATAJ • Department of Inorganic and Analytical Chemistry , University of Szeged ,

Szeged , Hungary ANTAL PÉTER • Department of Inorganic and Analytical Chemistry , University of Szeged ,

Szeged , Hungary MOHD MARSIN SANAGI • Department of Chemistry , Universiti Teknologi Malaysia , Johor ,

Malaysia ROCCALDO SARDELLA • Dipartimento di Chimica e Tecnologia del Farmaco , Università

degli Studi di Perugia , Perugia , Italy MARTIN G. SCHMID • Institute of Pharmaceutical Sciences, Karl-Franzens-University ,

Graz , Austria VOLKER SCHURIG • Institute of Organic Chemistry, University of Tübingen , Tübingen ,

Germany GERHARD K. E. SCRIBA • Department of Pharmaceutical/Medicinal Chemistry , Friedrich

Schiller University Jena , Jena , Germany ANNE-CATHERINE SERVAIS • Department of Pharmaceutical Sciences , University of Liège ,

Liège , Belgium

xviiContributors

SHAHAB A. SHAMSI • Department of Chemistry , Center of Biotechnology and Drug Design, Georgia State University , Atlanta , GA , USA

LIJUAN SONG • Chinese Academy of Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems , Beijing , China

DAVID A. SPIVAK • Department of Chemistry , Louisiana State University , Baton Rouge , LA , USA

TED J. SZCZERBA • Regis Technologies , Morton Grove , IL , USA GERALD TER FL OTH • GlaxoSmithKline Research and Development , King of Prussia ,

PA , USA TOSHIMASA TOYO’OKA • Graduate School of Pharmaceutical Sciences, University of Shizuoka ,

Shizuoka , Japan SHENGJIA WANG • Department of Pharmaceutical Analysis and Drug Metabolism ,

Zhejiang University , Hangzhou , China YONG WANG • Department of Chemistry , School of Sciences, Tianjin University ,

Tianjin , China GREGORY K. WEBSTER • Abbott Laboratories , Abbott Park , IL , USA DOROTHEE WISTUBA • Institute of Organic Chemistry, University of Tübingen ,

Tübingen , Germany SONG HEE YANG • Department of Chemistry , Inha University , Incheon , South Korea XIQIN YANG • GlaxoSmithKline Research and Development , King of Prussia , PA , USA LUSHAN YU • Department of Pharmaceutical Analysis and Drug Metabolism , Zhejiang

University , Hangzhou , China RUIJUAN YUAN • School of Chinese Pharmacy, Beijing University of Chinese Medicine ,

Beijing , China SU ZENG • Department of Pharmaceutical Analysis and Drug Metabolism , Zhejiang

University , Hangzhou , China TONG ZHANG • Chiral Technologies Europe , Illkirch , France ZHENBIN ZHANG • National Chromatographic R&A Center, Dalian Institute of Chemical

Physics , Dalian , China HANFA ZOU • National Chromatographic R&A Center, Dalian Institute of Chemical

Physics , Dalian , China