Review
Supercritical fluid chromatography for the 21st century

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Abstract

A brief historical review of supercritical fluid chromatography (SFC) as it pertains to open tubular (i.e. capillary) column SFC and packed column SFC is presented. Specific sections include (1) early emphasis on open tubular columns and non-polar analytes; (2) packed column SFC for separation of more polar analytes; (3) preparative scale packed column SFC. The review is completed by discussing current trends in SFC such as (a) chiral separations, (b) achiral separations, (c) simulated moving bed SFC, and (d) SFC coupled to mass spectrometry.

Graphical abstract

A brief historical review of supercritical fluid chromatography (SFC) as it pertains to open tubular (i.e. capillary) column SFC and packed column SFC is presented. Specific sections include (1) early emphasis on open tubular columns and non-polar analytes; (2) packed column SFC for separation of more polar analytes; (3) preparative scale packed column SFC. The review is completed by discussing current trends in SFC such as (a) chiral separations, (b) achiral separations, (c) simulated moving bed SFC, and (d) SFC coupled to mass spectrometry.

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Introduction

Supercritical fluids (SF) have densities and dissolving capacities similar to those of certain liquids, but lower viscosities and better diffusion properties. Accordingly, SF used as mobile phases in chromatography should act both as substance carriers like the mobile phases in gas chromatography (GC) and also dissolve these substances like the solvents in liquid chromatography (HPLC). This chromatographic variant is known as supercritical fluid chromatography (SFC). Klesper et al. are considered to be the discoverers of SFC [1]. They described in 1962 the separation of thermo-labile porphyrin derivatives using supercritical chlorofluoromethanes at pressures up to 140 bar and temperatures from 150 to 170 °C. This method was further developed both theoretically and experimentally later by other workers in the 1960s [2], [3]. Unfortunately, the development of SFC during this period was not comparable with the tempestuous growth of HPLC which occurred at about the same time. The initial major growth period for SFC, thus, occurred approximately 20-year later in the 1980s [4].

The renaissance of SFC is generally recognized to have come in 1981–1982 with Hewlett-Packard’s introduction of SFC instrumentation for packed column SFC at the Pittsburgh Conference and numerous subsequent studies by Berger [5] and Gere [6]. Concurrent with this event was the first report on the use of open tubular wall-coated capillary columns in SFC by Novotny et al. [7]. Capillary SFC, as popularized in the 1980s to almost the exclusion of packed column SFC, was practiced during this time using (1) capillary columns (50 μm i.d.), (2) a GC-like oven, (3) pure carbon dioxide, (4) a pump used as a pressure source to perform either pressure or density programming, (5) a fixed restrictor to maintain pressure in the column and to serve as an interface between the column outlet and the laboratory atmosphere, and (6) a flame ionization detector [8], [9], [10]. Historically, capillaries tended to be operated at temperatures well above the critical temperature of the fluid. Thus, this type of SFC was viewed as an extension of GC (but with a greater sample base) where some of the thermal energy required for mobilizing solutes was replaced with solvation energy. In contrast to conventional GC, capillary columns had significantly smaller inner diameters and stationary phases were more highly cross-linked. The most appropriate solutes tended to be homologous series of polymers and surfactants with moderate molecular weights up to approximately 10,000.

The reemergence of more user friendly packed column instrumentation and a switch in emphasis to more polar solutes such as pharmaceuticals and agrochemicals was delayed until the 1990s, and even then users largely relied on concepts developed in either GC or HPLC which were often inappropriate and misleading. Berger noted many times that “there are differences between supercritical fluids, gases, and liquids but they are not as dramatic as often supposed. In the final analysis, packed column SFC can be thought of as an odd form of HPLC, and furthermore, it has little in common with capillary SFC” [11]. The reader is referred to several reviews that discuss the progress of packed column SFC development during this period [12], [13]. The goal of this review, however, is to briefly trace the historical development of SFC in general and to describe the current state of the art.

Section snippets

Early emphasis on capillary columns

In 1984 a patent was surprisingly issued to Brigham Young University for a technique called “open tubular supercritical fluid chromatography” although several vendors argued at the time that the work was based primarily on prior art and the patent should be declared invalid [14]. Two years later, instrumentation for capillary SFC was introduced by several vendors at the Pittsburgh Conference. The primary thrusts during the 1980s came naturally from workers in the GC field rather than the HPLC

Packed columns rescue SFC

The other form of SFC uses packed columns, usually binary or ternary fluids, composition programming, and a UV detector. Stationary phases have much higher surface area to void volume ratios than capillaries and are thus much more retentive. Polar modifiers (which are usually incompatible with flame ionization detection) mixed with the main fluid (CO2) increase the solvating tendency and decrease the retention time of solutes. Once modifiers are added, mobile phase composition becomes more

Packed column SFC today

Nowadays, packed column SFC is widely accepted. It uses the same injector and packed column configurations as in HPLC. It is more robust and more adaptable to a broader spectrum of compound classes than just low molecular weight polymeric compounds and nonionic surfactants [11]. It thus is more useful for routine separation of pharmaceuticals for example than open tubular capillary column SFC. Difficulties with back-pressure regulation, consistent flow rates, modifier addition, sample

Preparative scale SFC

One of the most challenging problems encountered during the development of a new pharmaceutical compound is linked to purification. The synthesis schemes are more and more complex, and the request for rapid and efficient methods to isolate the target molecule from mixtures is crucial to ensure the success of the future drug. As far back as 1986, SFC was deemed to be ideal for a process instrument causing Combustion Engineering (Lewisburg, WV, USA) to design a “modern” process supercritical

Current trends

Major emphasis in SFC today concerns packed columns although several studies using open tubular columns continue to appear each year. Packed column SFC applications include (1) analytical scale chiral and achiral separations, (2) SFC coupled with mass spectrometric detection, (3) simulated moving bed, (4) natural product applications, and (5) preparative separations. A brief overview of each of these areas will afford the reader a snapshot of the current trends in the field.

Conclusion

In summary SFC (as most analytical techniques) has had a tortuous developmental history, but it appears that analytical and preparative scale SFC are currently on the strongest foundation ever with vendors that are strongly committed to advancing the technology. New developments and a broader spectrum of applications in the field are, however, anticipated in the future. It should be emphasized that the barriers between the various chromatographic techniques are imaginary and artificial. Chester

Acknowledgment

The assistance of Negin Nazem in the preparation of this manuscript is gratefully appreciated.

References (73)

  • P. Ramirez et al.

    Isolation of functional ingredients from rosemary by preparative supercritical fluid chromatography

    J. Pharm. Biomed. Anal.

    (2006)
  • S. Li et al.

    Efficient and scalable method in isolation of polymethoxyflavones from orange peel extract by supercritical fluid chromatography

    J. Chromatogr. B

    (2007)
  • S. Andersson et al.

    Preparative chiral chromatography and chiroptical characterization of enantiomers of omeprazole and related benzimidazoles

    Chirality

    (2007)
  • E. Klesper et al.

    High pressure gas chromatography above critical temperatures

    J. Org. Chem.

    (1962)
  • J.C. Giddings et al.

    Dense gas chromatography at pressures to 2000 atmospheres

    J. Chromatogr. Sci.

    (1969)
  • S.T. Sie et al.

    High-pressure gas chromatography and chromatography with supercritical fluids. II. Permeability and efficiency of packed columns with high-pressure gases as mobile phases under conditions of incipient turbulence

    Sep. Sci.

    (1967)
  • T.L. Chester

    The role of supercritical fluid chromatography in analytical chemistry

    J. Chromatogr. Sci.

    (1986)
  • T.A. Berger

    Packed Column SFC

    (1995)
  • D.R. Gere et al.

    Supercritical fluid chromatography: a technology update

    Fresenius J. Anal. Chem.

    (1988)
  • M. Novotny et al.

    Capillary supercritical fluid chromatography

    Anal. Chem.

    (1981)
  • D.W. Later et al.

    Capillary supercritical fluid chromatography, an emerging technology in perspective

    LC–GC

    (1986)
  • P.J. Schoenmakers et al.

    Supercritical fluid chromatography—recent and future developments

    Eur. Chromatogr. News

    (1987)
  • P.R. Griffiths

    Contemporary SFC: accomplishments and limitations

    Anal. Chem.

    (1988)
  • T.A. Berger

    Practical advantages of packed column supercritical fluid chromatography in supporting combinatorial chemistry

  • L.T. Taylor

    Packed column development in supercritical fluid chromatography

    J. Chromatogr. Sci.

    (1990)
  • L.T. Taylor

    Trends in supercritical fluid chromatography

    J. Chromatogr. Sci.

    (1997)
    D.E. Games et al.

    Packed and capillary column supercritical fluid chromatography/mass spectrometry

    Eur. Chromatogr. News

    (1987)
  • S. Hattangadi

    What’s wrong with BYU’s patent?

    Industrial Chemist

    (February 1987)
  • P. Schoenmakers

    Open columns or packed columns for supercritical fluid chromatography – a comparison

  • E. Klesper et al.

    Developments in supercritical fluid chromatography

    Chimicaoggi

    (November 1986)
  • R.M. Smith

    Supercritical fluids in separation science—the dreams, the reality, and the future

    J. Chromatogr.

    (1999)
  • K.W. Phinney

    SFC of drug enantiomers

    Anal. Chem.

    (2000)
  • C.M. Harris

    The SFC comeback

    Anal. Chem.

    (2002)
  • T.L. Chester

    Chromatography from the mobile-phase perspective

    Anal. Chem.

    (1997)
  • T.L. Chester et al.

    Supercritical fluid and unified chromatography

    Anal. Chem.

    (2004)
  • K.D. Bartle et al.

    Packed capillary column chromatography with gas, supercritical and liquid mobile phases

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