Supercritical eluent

Liquid phase chromatography can use a supercritical fluid as an eluent. The solvent evaporates on leaving the column and allows detection by FID. At present, there are few instances in the petroleum industry using the supercritical fluid technique. 

Supercritical fluid chromatography (SFC) provides a means of minimizing the limitations of CSPs developed for FC while retaining the impressive chiral selectivity that has been achieved through the evolution of CSPs during the past two decades [6, 7]. The use of supercritical fluids as eluents for chromatographic separations was... 

The use of both sub- and supercritical fluids as eluents yields mobile phases with increased diffusivity and decreased viscosity relative to liquid eluents [23]. These properties enhance chromatographic efficiency and improve resolution. Higher efficiency in SFC shifts the optimum flowrate to higher values so that analysis time can be reduced without compromising resolution [12]. The low viscosity of the eluent also reduces the pressure-drop across the chromatographic column and facilitates the... 

The high diffusivity and low viscosity of sub- and supercritical fluids make them particularly attractive eluents for enantiomeric separations. Mourier et al. first exploited sub- and supercritical eluents for the separation of phosphine oxides on a brush-type chiral stationary phase [28]. They compared analysis time and resolution per unit time for separations performed by LC and SFC. Although selectivity (a) was comparable in LC and SFC for the compounds studied, resolution was consistently... 

The efficiency of many CSPs increases dramatically when liquid eluents are replaced with sub- or supercritical fluids. During a comparison of LC and SFC performed with a Chiralcel OD CSP, Lynam and Nicolas reported that the number of theoretical plates obtained was three to five times higher in SFC than in LC [26]. The separation of metoprolol enantiomers by LC and SFC on a Chiralcel OD CSP is illustrated in Fig. 12-2. Although impressive selectivity is achieved by both techniques, resolution is higher in SFC (R = 12.7) than in LC (R = 4.8), and the higher flowrate in SFC reduces the analysis time. The increased efficiency of SFC also improves peak symmetry. 

A new brush-type CSP, the Whelk-0 1, was used by Blum et al. for the analytical and preparative-scale separations of racemic pharmaceutical compounds, including verapamil and ketoprofen. A comparison of LC and SFC revealed the superiority of SFC in terms of efficiency and speed of method development [50]. The Whelk-0 1 selector and its homologues have also been incorporated into polysiloxanes. The resulting polymers were coated on silica and thermally immobilized. Higher efficiencies were observed when these CSPs were used with sub- and supercritical fluids as eluents, and a greater number of compounds were resolved in SFC compared to LC. Compounds such as flurbiprofen, warfarin, and benzoin were enantioresolved with a modified CO, eluent [37]. 

Most supercritical fluid chromatographs use carbon dioxide as the supercritical eluent, as it has a convenient critical point of 31.3°C and 72.5 atmospheres. Nitrous oxide, ammonia and n-pentane have also been used. This allows easy control of density between 0.2g ml-1 and 0.8g ml-1 and the utilization of almost any detector from liquid chromatography or gas chromatography. 

SFC-NMR was used for the separation and identification of a mixture of five vitamin A acetate isomers using supercritical CO2 as the eluent [74], An advantage pointed out in this report is the lack of a solvent resonance, eliminating the need for solvent suppression and allowing unrestricted observation of the entire... 

Achieving suitable selectivity with pure CO2 might require too high a pressure, for polar compounds, so pure supercritical CO2 is often mixed with a co-solvent, modifier or entrainer. A correctly chosen co-solvent can increase both solvent power and selectivity of chromatographic separations, as shown in Figure 12.15, and will also strongly influence the solubility of the products in the selected eluent... 

The final approach to the reduction of eluent consumption is the optimal recycling of solvents. Indeed, preparative and industrial chromatography can be designed as a unit operation that includes solvent recycling dry feed mixture is injected while dry separated compounds are recovered. Many techniques can be applied depending on the situation in isocratic (that is with a constant mobile phase composition) or gradient conditions, and with organic and/or supercritical eluents. 

While a number of supercritical fluids (SC) are known and have been studied as reaction media, probably only SC-CO2 and water are of practical use in the synthesis of pharmaceutical intermediates. The application of SC-CO2 as a greener eluent for chromatography has been discussed in Chapter 12. This medium is also used as an extraction solvent and in API isolation, although its use at any scale... 

Equipment for supercritical fluid chromatography is similar to that for HPLC with packed columns12 or open tubular columns. Eluent strength is increased in HPLC by gradient elution and in gas chromatography by raising the temperature. In supercritical... 

SFC has received attention as an alternative separation technique to liquid and gas chromatography. The coupling of SFC to plasma detectors has been studied because plasma source spectrometry meets a number of requirements for suitable detection. There have been two main approaches in designing interfaces. The first is the use of a restrictor tube in a heated cross-flow nebuliser. This was designed for packed columns. For a capillary system, a restrictor was introduced into the central channel of the ICP torch. The restrictor was heated to overcome the eluent freezing upon decompression as it left the restrictor. The interface and transfer lines were also heated to maintain supercritical conditions. Several speciation applications have been reported in which SFC-ICP-MS was used. These include alkyl tin compounds (Oudsema and Poole, 1992), chromium (Carey et al., 1994), lead and mercury (Carey et al., 1992), and arsenic (Kumar et al., 1995). Detection limits for trimethylarsine, triphenylarsine and triphenyl arsenic oxide were in the range of 0.4-5 pg. 

Another emerging technology is supercritical fluid chromatography (SFC) that uses supercritical carbon dioxide as the apolar eluent [46]. The main advantage of SFC, which can be applied both in the analytical and in the purification area, is the higher resolution than the traditional HPLC, allowing time reduction and more efficient separations. Also this technique can be advantageously coupled with a MS detector, to further improve the full analytical process. 

---