Modern Supercritical Fluid Chromatography

Explains why modern supercritical fluid chromatography (SFC) is the leading "green" analytical and purification separations technology.

Modern supercritical fluid chromatography (SFC) is the leading method used to analyze and purify chiral and achiral chemical compounds, many of which are pharmaceuticals, pharmaceutical candidates, and natural products including cannabis-related compounds. This book covers current SFC instrumentation as it relates to greater robustness, better reproducibility, and increased analytical sensitivity.

Modern Supercritical Fluid Chromatography: Carbon Dioxide Containing Mobile Phases covers the history, instrumentation, method development and applications of SFC. The authors provided readers with an overview of analytical and preparative SFC equipment, stationary phases, and mobile phase choices. Topics covered include: Milestones of Supercritical Fluid Chromatography; Physical Properties of Supercritical Fluids; Instrumentation for SFC; Detection in SFC; Achiral SFC Method Development; Chiral SFC Method Development; and Preparative Scale SFC. The book also includes highlights of modern applications of SFC in the final chapters--namely pharmaceuticals, consumer products, foods, polymers, petroleum-related mixtures, and cannabis--and discusses the future of SFC.

• Provides a clear explanation of the physical and chemical properties of supercritical fluids, which gives the reader a better understanding of the basis for improved performance in SFC compared to HPLC and GC

• Describes the advantages of SFC as a green alternative to HPLC and GC for the analysis of both polar, water-soluble, and non-polar analytes

• Details both achiral and chiral SFC method development, including modifiers, additives, the impact of temperature and pressure, and stationary phase choices

• Details why SFC is the premier modern preparative chromatographic technique used to purify components of mixtures for subsequent uses, both from performance and economic perspectives

• Covers numerous detectors, with an emphasis on SFC-MS, SFC-UV, and SFC-ELSD (evaporative light scattering detection)

• Describes the application of SFC to numerous high-value application areas

Modern Supercritical Fluid Chromatography: Carbon Dioxide Containing Mobile Phases will be of great interest to professionals, students, and professors involved in analytical, bioanalytical, separations science, medicinal, petroleum, and environmental chemistries. It will also appeal to pharmaceutical scientists, natural-product scientists, food and consumer-products scientists, chemical engineers, and managers in these areas.

Autorentext

LARRY M. MILLER is Principal Scientist at Amgen in Cambridge, MA, and is the author or co-author of more than 30 peer reviewed publications and two book chapters. J. DAVID PINKSTON, PHD, is Technical Services Manager at Archer Daniels Midland in Decatur, IL and the author or co-author of over 60 peer-reviewed publications and book chapters. LARRY T. TAYLOR, PHD, is Emeritus Professor of Chemistry at Virginia Tech in Blacksburg, VA, and the author or co-author of more than 400 peer-reviewed publications, books, and book chapters.

Inhalt
Preface xiii

1 Historical Development of SFC 1

1.1 Physical Properties of Supercritical Fluids 1

1.2 Discovery of Supercritical Fluids (18221892) 6

1.3 Supercritical Fluid Chromatography (19621980) 8

1.4 SFC with Open Tubular Columns (19801992) 15

1.5 Rediscovery of pcSFC (19922005) 19

1.6 Modern Packed Column SFC 22

References 24

2 Carbon Dioxide as the Mobile Phase 29

2.1 Introduction to Carbon Dioxide 29

2.2 Supercritical Carbon Dioxide 32

2.3 Solvating Power of Supercritical CO2 35

2.4 Solvating Power of Modified CO2 45

2.5 Clustering of CO2 49

References 52

3 Instrumentation for Analytical Scale Packed Column SFC 55

3.1 Introduction 56

3.2 Safety Considerations 56

3.3 Fluid Supply 58

3.3.1 Carbon Dioxide and Other Compressed Gases 58

3.3.2 Mobile Phase Modifiers and Additives 59

3.4 Fluid Delivery Pumps and Pumping Considerations 60

3.4.1 Pump Thermostating 60

3.4.2 Fluid Pressurization and Metering 60

3.4.3 Modifier Fluid Pumping 61

3.4.4 Pressure and Flow Ranges 62

3.4.5 Fluid Mixing 62

3.5 Sample Injection and Autosamplers 62

3.6 Tubing and Connections 64

3.6.1 Tubing 64

3.6.1.1 Stainless Steel Tubing 64

3.6.1.2 Polymeric Tubing 65

3.6.2 Connections 66

3.7 Column and Mobile Phase Temperature Control 66

3.8 Chromatographic Column Materials of Construction 67

3.9 Backpressure Regulation 68

3.9.1 Passive Flow Restriction 69

3.9.2 Active Backpressure Regulation 70

3.10 Waste Disposal 72

3.11 Conclusion 72

References 72

4 Detection in Packed Column SFC 77

4.1 Introduction 78

4.2 Predecompression Detection (CondensedFluidPhase Detection) 78

4.2.1 UV/VIS Absorbance 78

4.2.2 Fluorescence Detection 81

4.2.3 Electrochemical Detection 82

4.2.4 Other Less Common Condensed Phase Detectors 83

4.2.4.1 FlowCell Fourier Transform InfraRed Absorbance (FTIR) Detection 83

4.2.4.2 Online Nuclear Magnetic Resonance (NMR) Detection 84

4.2.4.3 Refractive Index (RI) Detection 85

4.3 Postdecompression Detection (Gas/Droplet Phase Detection) Interfacing Approaches 85

4.3.1 Pre-BPR Flow Splitting 86

4.3.2 Total Flow Introduction (Post-BPR Detection) 88

4.3.2.1 BPR Requirements for TotalFlow Introduction Detection 88

4.3.2.2 Total Flow Introduction with Mechanical BPR 89

4.3.2.3 Total Flow Introduction PressureRegulatingFluid (PRF) Interface 89

4.3.2.4 Total Flow Introduction without Active Backpressure Regulation 91

4.4 Postdecompression Detection 93

4.4.1 FlameBased Detectors 93

4.4.2 Evaporative Light Scattering Detection (ELSD) and Charged Aerosol Detection (Corona CAD) 97

4.4.3 Mass Spectrometric Detection 98

4.4.3.1 Interfacing and Ionization Approaches 99

4.4.3.2 Atmospheric Pressure Chemical Ionization (APCI) 100

4.4.3.3 Pneumatically Assisted Electrospray Ionization (ESI) 101

4.4.3.4 Atmospheric Pressure Photoionization (APPI) 103

4.4.4 Postdecompression Detection Using Less Common Approaches Deposition IR 103

4.5 Concluding Remarks 103

References 104

5 Chiral Analytical Scale SFC Method Development, Stationary Phases, and Mobile Phases 117

5.1 Introduction 117

5.2 Chiral Stationary Phases for SFC 119

5.3 Chiral SFC vs. Chiral HPLC 128

5.4 Method Development Approaches 130

5.4.1 Modifiers for Chiral SFC 132

5.4.2 Additives for Chiral SFC 133

5.4.3 Nontraditional Modifiers 135

5.4.4 Method Development Approaches 137 5.5 High Throughput Method Develop...