Applications of Ion Chromatography for Pharmaceutical and Biological Products

This is a comprehensive source of information on the application of ion chromatography (IC) in the analysis of pharmaceutical drugs and biologicals. This book, with contributors from academia, pharma, the biotech industry, and instrument manufacturing, presents the different perspectives, experience, and expertise of the thought leaders of IC in a comprehensive manner. It explores potential IC applications in different aspects of product development and quality control testing. In addition, an appendix section gives information on critical physical and chromatographic parameters related to IC and information on current manufacturers of IC systems, columns, and other components.

Contributors ix

Preface xi

Part I Principles, Mechanism, and Instrumentation 1

1 Ion Chromatography—principles and Applications 3
Lokesh Bhattacharyya

2 Retention Processes in Ion-exclusion Chromatography: a New Perspective 23
Milko Novič and Paul R. Haddad

3 Pulsed Electrochemical Detection in Ion Chromatography 49
William R. LaCourse

4 Suppressor Design and Detection for Ion Chromatography 91
Kannan Srinivasan, Sheetal Bhardwaj, Rong Lin, and Christopher Pohl

5 Modelling and Optimization of Ion Chromatographic Separations of Pharmaceutically RelevantOrganic Ions 107
Philip Zakaria, Greg Dicinoski, Melissa Hanna-Brown, and Paul R. Haddad

Part II Pharmaceutical Applications 135

6 Ion Chromatography in Pharmaceutical Drug Analysis 137
Lokesh Bhattacharyya

7 Analysis for Impurities by Ion Chromatography 159
Shreekant V. Karmarkar

8 Ion Chromatography Analysis of Aminoglycoside Antibiotics 175
Valoran P. Hanko and Jeffrey S. Rohrer

9 Use of Cation-exchange Ion Chromatography in the Analysis of Pharmaceuticals 193
Christopher Pohl, Maria Rey, and Rosanne Slingsby

10 Comprehensive Approaches for Measurement of Active Pharmaceutical Ingredients, Counter-ions,and Excipients Using HPLC with Charged Aerosol Detection 221
Christopher Crafts, Bruce Bailey, Paul Gamache, Xiaodong Liu, and Ian Acworth

11 High Performance Ion Chromatographic Analysis of Cholinergic Compounds: Carbachol andBethanechol, and Associated Degradation Products 237
David Trowbridge

12 Ion Chromatographic Analysis of Pharmaceuticals for Authenticity and Adulteration 247
David S. Jackson

13 Ion Chromatography of Drug Product Counter-ions and other Ions in Drug Products 259
Brian M. De Borba and Jeffrey S. Rohrer

14 Sample Preparation Techniques in Ion Chromatography for Pharmaceutical Applications 271
Jay Gandhi

15 Validation of Ion Chromatographic Methods 285
Shreekant V. Karmarkar

16 Pharmacopeial Applications of Ion Chromatography 309
Ravi Ravichandran

Part III Biotechnology Applications 321

17 Glycan Analysis by High Performance Anion Exchange Chromatography with Pulsed AmperometricDetection 323
Lokesh Bhattacharyya

18 Monosaccharide Analysis of Glycoproteins By High-performance Anion-exchange Chromatographywith Pulsed Amperometric Detection 339
Jeffrey S. Rohrer

19 Two-dimensional Ion Chromatography for Simultaneous Determination of Amino Acids andCarbohydrates 351
Petr Jandik and Jun Cheng

20 Monitoring Protein N-glycosylation Consistency Using Hpaec-pad 365
Carl Grey

21 Oligosaccharide Analysis by High-performance Anion-exchange Chromatography Hyphenated toIntegrated Pulsed Amperometric Detection and On-line Ion-trap Mass Spectrometry 379
Cees Bruggink

Part IV Vaccine Applications 393

22 Applications of Ion Chromatography in Biological Product Analyses 395
Alfred V. Del Grosso and Brandon Duong

23 High Performance Anion-exchange Chromatography With Pulsed Amperometric Detection (hpaec-pad) Analysis of Gbs Glycoconjugate Vaccines: From Fermentation to Final Product 423
Stefano Ricci, Barbara Fabbri, Sara Giannini, Silvia Bernardini, Marcello Morelli, and Sandro D’Ascenzi

24 Stability Studies and Characterization of Meningococcal A, C, Y, and W 135 Glycoconjugate Vaccine435
Valeria Carinci, Alberto Bernardini, Cristiana Campa, Claudia Magagnoli, Francesca Beccai, and Sandro D’Ascenzi

Part V Appendices 449

Appendix 1 DISSOCIATION CONSTANTS (pK_a) OF ORGANIC Acids (at 20^◦C) 451

Appendix 2 DISSOCIATION CONSTANTS (pK_a) OF COMMON Sugars and Alcohols 455

Index 457

“This book is a model of what can be achieved with a well-developed plan and the support of expert authors.” (Chromatographia, 2012)

Lokesh Bhattacharyya is a Lab Chief at the Center for Biologics Evaluation and Research (CBER) at the U.S. Food and Drug Administration (FDA). Prior to beginning his FDA work in 2006, he had over fourteen years of industry experience as an analytical chemist and biochemist. Dr. Bhattacharyya has thirty-nine papers, nine review articles, and nearly thirty conferences as speaker or session chair to his credit.

Jeffrey S. Rohrer is the Director of Applications Development for Thermo Fisher Scientific, Dionex Products. In this position he directs the work of three corporate applications laboratories in California, China, and Thailand. These labs develop HPLC, IC, HPAE-PAD, and other LC-based assays. Dr. Rohrer is an author of over fifty peer-reviewed publications. He is also a member of the United States Pharmacopeia Expert Committee on Monograph Development for Antibiotics, Antivirals, and Antimicrobials.

Thorough coverage of the applications of ion chromatography to the analysis of pharmaceutical drugs and biologicals

Since its introduction in the mid-1970s, ion chromatography (IC), a high-performance liquid chromatography technique, has developed into an important analytical methodology for a number of applications in the pharmaceutical, biotechnology, and environmental industries.

With contributors from academia, the pharmaceutical and biotech industries, and instrument manufacturers, this book takes a comprehensive approach to this steadily growing field to present different perspectives, experiences, and expertise influencing the development of IC.

This book features:

• Potential IC applications in different aspects of development, characterization, and quality control testing of pharmaceutical and biological drug products, and vaccines

• Recent advances in IC technology and applications, case studies, investigations and trouble-shooting experiences, and issues of current regulatory compliance

• An appendix with critical physical and chromatographic parameters related to IC

• A close look at technology that has permitted IC to be coupled with mass spectrometry, which is a critical milestone for a wider interest in IC as a product characterization tool

A valuable learning tool for beginners and a comprehensive reference for seasoned professionals, Applications of Ion Chromatography for Pharmaceutical and Biological Products brings important new insight to pharmaceutical and biotechnology science.