ReviewSupercritical fluid chromatography for the 21st century
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.
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)
- et al.
High pressure gas chromatography of nonvolatile species
Science
(1968) - et al.
Analysis of artemisinin by a packed-column supercritical fluid chromatography-atmospheric pressure chemical ionization mass spectrometry technique
Analyst
(2003) - et al.
Enantiomeric separation of chiral sulfoxides by supercritical fluid chromatography
J. Sep. Sci.
(2006) - et al.
Comparison of supercritical fluid chromatography and liquid chromatography for the separation of urinary metabolites of nobiletin with chiral and non-chiral stationary phases
Biomed. Chromatogr.
(2006) - et al.
Feasibility of phospholipids separation by packed column SFC with mass spectrometric and light scattering detection
Chromatographia
(2007) - et al.
Preparative chromatography with supercritical fluids: comparison of simulated moving bed and batch process
J. Chromatogr. A
(2007) - et al.
Simulated moving columns technique for enantioselective supercritical fluid chromatography
Chirality
(2007) - et al.
Separation of coenzyme Q10 in palm oil by supercritical fluid chromatography
Am. J. Appl. Sci.
(2006) - et al.
Exploration of liquid and supercritical fluid chromatographic chiral separation and purification of nutlin-3—a small molecule antagonist of MDM2
J. Pharm. Biomed. Anal.
(2007)
Isolation of functional ingredients from rosemary by preparative supercritical fluid chromatography
J. Pharm. Biomed. Anal.
Efficient and scalable method in isolation of polymethoxyflavones from orange peel extract by supercritical fluid chromatography
J. Chromatogr. B
Preparative chiral chromatography and chiroptical characterization of enantiomers of omeprazole and related benzimidazoles
Chirality
High pressure gas chromatography above critical temperatures
J. Org. Chem.
Dense gas chromatography at pressures to 2000 atmospheres
J. Chromatogr. Sci.
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.
The role of supercritical fluid chromatography in analytical chemistry
J. Chromatogr. Sci.
Packed Column SFC
Supercritical fluid chromatography: a technology update
Fresenius J. Anal. Chem.
Capillary supercritical fluid chromatography
Anal. Chem.
Capillary supercritical fluid chromatography, an emerging technology in perspective
LC–GC
Supercritical fluid chromatography—recent and future developments
Eur. Chromatogr. News
Contemporary SFC: accomplishments and limitations
Anal. Chem.
Practical advantages of packed column supercritical fluid chromatography in supporting combinatorial chemistry
Packed column development in supercritical fluid chromatography
J. Chromatogr. Sci.
Trends in supercritical fluid chromatography
J. Chromatogr. Sci.
Packed and capillary column supercritical fluid chromatography/mass spectrometry
Eur. Chromatogr. News
What’s wrong with BYU’s patent?
Industrial Chemist
Open columns or packed columns for supercritical fluid chromatography – a comparison
Developments in supercritical fluid chromatography
Chimicaoggi
Supercritical fluids in separation science—the dreams, the reality, and the future
J. Chromatogr.
SFC of drug enantiomers
Anal. Chem.
The SFC comeback
Anal. Chem.
Chromatography from the mobile-phase perspective
Anal. Chem.
Supercritical fluid and unified chromatography
Anal. Chem.
Packed capillary column chromatography with gas, supercritical and liquid mobile phases
Cited by (254)
A nitrogenous heterocyclic ring-bonded stationary phase for separating alkaloids in supercritical fluid chromatography
2024, Journal of Chromatography ADiscrimination of plastic waste pyrolysis oil feedstocks using supercritical fluid chromatography
2024, Journal of Chromatography AModeling solid solute solubility in supercritical carbon dioxide by machine learning algorithms using molecular sigma profiles
2024, Journal of Molecular LiquidsAdvances in membrane-based chiral separation
2023, Coordination Chemistry ReviewsA novel switchable water stationary phase for supercritical fluid chromatography
2023, Analytica Chimica Acta