Modern Supercritical Fluid Chromatography

Carbon Dioxide Containing Mobile Phases

Larry M. Miller, J. David Pinkston, Larry T. Taylor

• Publisher: Wiley
• Year: 2019
• Print ISBN: 9781118948392
• eBook ISBN: 9781119626008
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Analytic Chemistry

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.

1
Historical Development of SFC

---

OUTLINE

1. 1.1 Physical Properties of Supercritical Fluids
2. 1.2 Discovery of Supercritical Fluids (1822–1892)
3. 1.3 Supercritical Fluid Chromatography (1962–1980)
4. 1.4 SFC with Open Tubular Columns (1980–1992)
5. 1.5 Rediscovery of pcSFC (1992–2005)
6. 1.6 Modern Packed Column SFC
7. References

---

1.1 Physical Properties of Supercritical Fluids

In supercritical fluid chromatography (SFC), the mobile phase is ideally in the supercritical state. The meaning of the word supercritical (literally, above critical) is explained in Figure 1.1. The figure shows a phase diagram for a single (pure) component. Depending on the temperature (T) and the pressure (P), three different states of matter may be distinguished. These are gas (G), liquid (L), and solid (S) states. At the triple point (tp) all three of these phases may coexist. Above the critical point (cp) a difference between gaseous and liquid states can no longer be observed. This region is illustrated in Figure 1.1 by the dashed lines, which defines the supercritical fluid region and the material is referred to as a supercritical fluid (Schoenmakers, P.J. and Uunk, L.G.M., “Mobile and stationary phases for supercritical fluid chromatography,” Private Communication.).

The supercritical fluid region is not a fourth state of matter. Crossing one of these dashed lines does not result in a phase change, whereas crossing a solid line does. Both condensation and evaporation are phase changes, during which the physical properties (e.g. density, viscosity, and diffusivity) change abruptly. On the other hand, a gas can also be transformed into a liquid in a manner indicated by the curved arrow in Figure 1.1. During this process, a phase change is not observed; yet, gas is transformed into a liquid. More generally stated, the physical properties of a pure compound show continuous rather than abrupt variations when passing through one of the dash lines.

Figure 1.1 Phase diagram for a single pure component, illustrating areas in which solid (S), liquid (L), gaseous (G), and supercritical (SF) conditions occur. tp is the triple point and cp is the critical point. A gas can be transferred into a liquid by following the arrow. In doing so, the density, the viscosity, and the diffusion coefficient change continuously from gas‐like to liquid‐like values, but no phase change is observed.

Source: Schoenmakers [1, p. 102].

The region of the phase diagram at temperatures and pressures higher than the critical temperature and critical pressure values was formally (and arbitrarily) designated as the supercritical fluid region by both the American Society for Testing and Materials (ASTM) and by the International Union of Pure and Applied Chemistry (IUPAC) (see Figure 1.2). This designation introduced what appears to be a fourth state of matter, the supercritical fluid. A second designation can be found in Figure 1.3 wherein two subcritical regions are identified along with the supercritical fluid region. Chester has cautioned that this format is an immense source of confusion among novices and even some experts [4]. In this diagram, the supercritical fluid region is formally defined as shown, however the apparent boundaries are not phase transitions, only arbitrary definitions.

The literature is full of statements regarding the transition between a liquid and a supercritical fluid phase or between a vapor and a supercritical fluid phase. This is incorrect according to Chester. A discontinuous phase change is predicted when the boiling line is crossed, but no discontinuous transitions or phase changes take place for isothermal pressure changes above the critical temperature or for isobaric temperature changes above the critical pressure. There are no transitions into or out of a supercritical fluid state even though the supercritical fluid region is defined formally according to Chester.

Figure 1.2 Definition of supercritical fluid by American Society for Testing and Materials (ASTM) and International Union of Pure and Applied Chemistry (IUPAC).

Source: Smith [2]; ASTM [3]; Chester [4, vol. 2, p. 11, figure 2].

Figure 1.3 Misleading phase diagram for a single component supercritical fluid.

Source: Laboureur et al. [5]. https://www.mdpi.com/1422‐0067/16/6/13868. Licenced under CC BY 4.0.

In other words, it is possible to convert a liquid to a vapor, or a vapor to a liquid, without undergoing a discontinuous phase transition by choosing a pressure/temperature path that is wholly within the continuum. The required path simply goes around the critical point and avoids going through the boiling line. The distinction between liquid and vapor simply ceases for temperatures and pressures beyond the critical point [6]. As stated previously, Figure 1.1 is the accurate depiction of phase behavior. There is no fundamental difference between supercritical fluids and gases or liquids. Rather, a supercritical fluid may best be thought of as a very dense gas!

A more useful description of supercritical fluids for chromatographers is shown in Figure 1.4. In chromatography, multi‐component supercritical mobile phases are frequently employed instead of a pure supercritical fluid. It is useful to continue thinking of the fluid phase behavior, but this requires one to expand the phase diagram to include the composition variation possible in a binary mobile phase [7]. Six general types of binary‐mixture systems have been ...

Table of contents

• Cover
• Table of Contents
• Chemical Analysis
• Preface
• 1 Historical Development of SFC
• 2 Carbon Dioxide as the Mobile Phase
• 3 Instrumentation for Analytical Scale Packed Column SFC
• 4 Detection in Packed Column SFC
• 5 Chiral Analytical Scale SFC – Method Development, Stationary Phases, and Mobile Phases
• 6 Achiral Analytical Scale SFC – Method Development, Stationary Phases, and Mobile Phases
• 7 Instrumentation for Preparative Scale Packed Column SFC
• 8 Preparative Achiral and Chiral SFC – Method Development, Stationary Phases, and Mobile Phases
• 9 Impact and Promise of SFC in the Pharmaceutical Industry
• 10 Impact of SFC in the Petroleum Industry
• 11 Selected SFC Applications in the Food, Polymer, and Personal Care Industries
• 12 Analysis of Cannabis Products by Supercritical Fluid Chromatography
• 13 The Future of SFC
• Index
• Chemical Analysis
• End User License Agreement