Separation Methods in Drug Synthesis and Purification

Preface
Klara Valko

1. Comparison of various modes and phase systems for analytical HPLC

Pavel Jandera

1.1 Fundamentals of high-performance liquid chromatography

1.2 High-performance liquid chromatography separation medi

1.3 Separation modes in high-performance liquid chromatography

1.4 Method development and optimization of separation conditions

2. Fast-generic HPLC methods

Ian M. Mutton

2.1 Introduction

2.2 Theory

2.3 Strategy for production of fast gradients

2.4 Fast gradients in practice

2.5 Conclusions

3. Advances in capillary electrochromatography

José Luís Dores-Sousa, Jelle De Vos, Debby Mangelings and Sebastiaan Eeltink

3.1 Introduction

3.2 The electroosmotic flow

3.3 Separation efficiency and kinetic performance limits

3.4 Retention

3.5 Instrument setup

3.6 Column technology

3.7 (Bio)pharmaceutical and biochemical applications

3.8 Concluding remarks

List of abbreviations and symbols

4. Coupled chromatographyemass spectrometry techniques for the analysis of combinatorial libraries

Steve Lane

4.1 Introduction

4.2 LC/MS analysis of high-throughput parallel synthesis libraries

4.3 Example for monitoring the rehearsal phase of the synthesis of  a solid-phase library

4.4 LC/UV/MS as a prescreen for Autoprep solution phase

4.5 Assisted automated LC/MS analysis

4.6 The analysis of split-pool combinatorial libraries

4.7 Industrialization of the process

4.8 Conclusions and future

5. Experimental design-based optimization strategies for chromatographic and capillary electrophoretic separations

J. Viaene and Y. Vander Heyden

5.1 Introduction

5.2 Main factors affecting separation

5.3 Responses and response functions

5.4 Univariate optimization strategies

5.5 Simplex sequential approach

5.6 Factorial methods

5.7 Multicriteria decision-making methods

5.8 Peculiarities of optimizing separations: optimizing resolution

5.9 Automating the entire process: expert systems and knowledge-based systems

5.10 Transfer of optimized capillary electrophoresis methods

5.11 Conclusions

6. Computer-aided HPLC method development for quality control of complex drug mixtures--An application example for DryLab

Halina Katsialevich, Hans-Jürgen Rieger, Imre Molnár and Arnold Zöldhegyi

6.1 Introduction

6.2 Experimental part

6.3 Method development using the DryLab4 software

6.4 Summary

7. The flexible application of automated preparative purification platforms within drug discovery

Jennifer Kingston, Neil Sumner, Katie Proctor and Elisabetta Chiarparin

7.1 Introduction

7.2 Reverse-phase high-performance liquid chromatography as a robust chromatographic tool

7.3 HPLC purification within drug discovery

7.4 Evolution of supercritical fluid chromatography as a robust purification platform

7.5 Multi-parallel synthesis purification processes at AstraZeneca

7.6 Flexible use of HPLC and SFC as orthogonal separation techniques

8. Strategies for the development of process chromatography as a unit operation for the pharmaceutical industry

Drew Katti

8.1 Introduction

8.2 The process development cycle

8.3 Chromatographic unit operations

8.4 Discovery experiment stage

8.5 Development stage

8.6 Modes of chromatography

8.7 Overloaded elution chromatography-isocratic mode

8.8 Economics of overloaded elution chromatography

8.9 Simulated moving bed chromatography

8.10 Chromatography techniques make a comes back

8.11 Safety and environmental

8.12 Regulatory and compliance

8.13 Conclusion

9. Recent developments in liquid and supercritical fluid chromatographic enantioseparations

Debby Mangelings, Sebastiaan Eeltink and Yvan Vander Heyden

9.1 Stereochemistry in a pharmaceutical environment

9.2 Enantioseparations of racemates in liquid chromatography and sub/supercritical fluid chromatography

9.3 Scope and aims

9.4 Direct enantioseparations with chiral mobile phase additives

9.5 Direct enantioseparations: chiral stationary phases

9.6 Conclusions

10. Basis and pharmaceutical applications of thin-layer chromatography

Huba Kalász, Mária Báthori and Klára Valko

10.1 Planar chromatography

10.2 The components of the planar stationary phase

10.3 Mobile phases for thin-layer chromatography

10.4 The chambers

10.5 Detection

10.6 Application of thin-layer chromatography in pharmaceutical and forensic analysis

10.7 Future developments, Quo Vadis thin-layer chromatography

11. Recent advances in quantitative structureeretention relationships

Roman Kaliszan

11.1 Introduction

11.2 Strategy of quantitative structureeretention relationship research

11.3 Retention prediction

11.4 Molecular mechanism of retention in view of quantitative structureeretention relationship

11.5 Chromatographic methods of determination of hydrophobicity

11.6 Applications of quantitative structureeretention relationship in molecular pharmacology and rational drug design

11.7 Concluding remarks

12. Capillary electrophoresis for drug analysis and physicochemical characterization

Susana Amézqueta, Xavier Subirats, Elisabet Fuguet, Clara Ràfols and Martí Rosés

12.1 Introduction to capillary electrophoresis

12.2 Buffers in capillary electrophoresis

12.3 Capillary zone electrophoresis

12.4 Nonaqueous capillary electrophoresis

12.5 Introduction to micellar electrokinetic chromatography

12.6 Introduction to microemulsion and liposome electrokinetic chromatography

13. Application of HPLC measurements for the determination of physicochemical and biomimetic properties to model in vivo drug distribution in support of early drug discovery

Klára L. Valkó

13.1 Introduction

13.2 Measurements of compound lipophilicity using chromatography

13.3 Measurement of membrane binding by immobilized artificial membrane high-performance liquid chromatography

13.4 Measurement of drug-protein binding constants by high-performance liquid chromatography

13.5 Measurements of solubility by high-performance liquid chromatography

13.6 Measurement of acid-base character by high-performance liquid chromatography

13.7 Measurements of H-bond acidity, basicity and polarizability/dipolarity by high-performance liquid chromatography

13.8 Application of chromatographic properties in drug discovery

13.9 Conclusion