Investigation of retention behavior of drug molecules in supercritical fluid chromatography using linear solvation energy relationships (original) (raw)
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Journal of Chromatography A, 2013
In supercritical fluid chromatography (SFC), the effects of adding a co-solvent to carbon dioxide are numerous. In this work, the changes in retention and selectivity occurring when the nature of the cosolvent (methanol, ethanol, isopropanol, acetonitrile) in the SFC mobile phase is varied, are studied on seven columns with different stationary phase chemistry (cyanopropyl-, pyridine-ethyl-, phenyloxypropyl-, phenyl-propyl-, phenyl-hexyl-, pentafluorophenyl-propyl-and octadecyl-bonded silica). Hierarchical cluster analysis and quantitative structure-retention relationships with the solvation parameter model are employed to evaluate these effects, based on the observed retention for over a hundred probe compounds. It appears that some columns are somewhat more affected than others by the change of solvent nature. Acetonitrile induces the strongest differences, essentially due to its poor capabilities as an eluent for bases and possibly because it does not adequately cover residual silanol groups. Ethanol appears to be a possible green alternative to the most-used methanol. Some hints on a possible partition-adsorption mixed mechanism are offered. Finally, sample applications with three different test mixtures relevant to cosmetic and pharmaceutical applications (flavanones, non-steroidal anti-inflammatory drugs and barbiturates) are presented.
Supercritical fluid chromatography in pharmaceutical analysis
Journal of pharmaceutical and biomedical analysis, 2015
In the last few years, there has been a resurgence of supercritical fluid chromatography (SFC), which has been stimulated by the introduction of a new generation of instruments and columns from the main providers of chromatographic instrumentation, that are strongly committed to advancing the technology. The known limitations of SFC, such as weak UV sensitivity, limited reliability and poor quantitative performance have been mostly tackled with these advanced instruments. In addition, due to the obvious benefits of SFC in terms of kinetic performance and its complementarity to LC, advanced packed-column SFC represents today an additional strategy in the toolbox of the analytical scientist, which may be particularly interesting in pharmaceutical analysis. In the present review, the instrumentation and experimental conditions (i.e. stationary phase chemistry and dimensions, mobile phase nature, pressure and temperature) to perform "advanced SFC" are discussed. The applicabil...
Supercritical fluid chromatography in drug analysis: a literature survey
Analytical and Bioanalytical Chemistry, 1996
The applications of supercritical fluid chromatography to the analysis of drugs have been carefully revised from the literature compiled in the Analytical Abstracts until March 1994. Easy-to-read tables provide useful information about the state-of-the-art and possibilities offered by SFC in pharmaceutical analysis. The tables comprise extensive data about samples analyzed, pharmaceutical principles determined, solvents used and sample quantity injected, supercritical fluids and modifiers employed, injection system, instrumentation, experimental conditions for chromatographic separations (density, pressure, flow, temperature), characteristics of columns employed (type, support, length, diameter, particle film thickness, stationary phase), detectors, type of restrictors, and also some analytical features of the methods developed (such as retention time, resolution, sensitivity, limit of detection and relative standard deviation).
Journal of Chromatography A, 1992
The separation of oligomers of two different polymers using capillary supercritical fluid chromatography was studied. Pressure programming was used to achieve optimum separation of the oligomers. From a comparison of the separation of these oligomers with different length columns it was demonstrated that oligomer solubility was primarily controlling the separation. Accordingly, changing the stationary phase, shortening the column or not even using a stationary phase had minimal effect on the separation of the oligomers.
Journal of chromatography. A, 2015
Impurity profiling of organic products that are synthesized as possible drug candidates requires complementary analytical methods to ensure that all impurities are identified. Supercritical fluid chromatography (SFC) is a very useful tool to achieve this objective, as an adequate selection of stationary phases can provide orthogonal separations so as to maximize the chances to see all impurities. In this series of papers, we have developed a method for achiral SFC-MS profiling of drug candidates, based on a selection of 160 analytes issued from Servier Research Laboratories. In the first part of this study, focusing on mobile phase selection, a gradient elution with carbon dioxide and methanol comprising 2% water and 20mM ammonium acetate proved to be the best in terms of chromatographic performance, while also providing good MS response [1]. The objective of this second part was the selection of an orthogonal set of ultra-high performance stationary phases, that was carried out in ...
Journal of analytical methods in chemistry, 2017
Retention mechanisms involved in supercritical fluid chromatography (SFC) are influenced by interdependent parameters (temperature, pressure, chemistry of the mobile phase, and nature of the stationary phase), a complexity which makes the selection of a proper stationary phase for a given separation a challenging step. For the first time in SFC studies, Parallel Factor Analysis (PARAFAC) was employed to evaluate the chromatographic behavior of eight different stationary phases in a wide range of chromatographic conditions (temperature, pressure, and gradient elution composition). Design of Experiment was used to optimize experiments involving 14 pharmaceutical compounds present in biological and/or environmental samples and with dissimilar physicochemical properties. The results showed the superiority of PARAFAC for the analysis of the three-way (column × drug × condition) data array over unfolding the multiway array to matrices and performing several classical principal component a...
Journal of Chromatography A, 2014
The recent market release of a new generation of supercritical fluid chromatography (SFC) instruments compatible with state-of-the-art columns packed with sub-2 m particles (UHPSFC) has contributed to the reemergence of interest in this technology at the analytical scale. However, to ensure performance competitiveness of this technique with modern analytical standards, a robust hyphenation of UHPSFC to mass spectrometry (MS) is mandatory. UHPSFC-MS hyphenation interface should be able to manage the compressibility of the SFC mobile phase and to preserve as much as possible the chromatographic separation integrity. Although several interfaces can be envisioned, each will have noticeable effects on chromatographic fidelity, flexibility and user-friendliness. In the present study, various interface configurations were evaluated in terms of their impact on chromatographic efficiency and MS detection sensitivity. An interface including a splitter and a make-up solvent inlet was found to be the best compromise and exhibited good detection sensitivity while maintaining more than 75% of the chromatographic efficiency. This interface was also the most versatile in terms of applicable analytical conditions. In addition, an accurate model of the fluidics behavior of this interface was created for a better understanding of the influence of chromatographic settings on its mode of operation. In the second part, the most influential experimental factors affecting MS detection sensitivity were identified and optimized using a design-of-experiment approach. The application of low capillary voltage and high desolvation temperature and drying gas flow rate were required for optimal ESI ionization and nebulization processes. The detection sensitivity achieved using the maximized UHPSFC-ESI-MS/MS conditions for a mixture of basic pharmaceutical compounds showed 4-to 10-fold improvements in peak intensity compared to the best performance achieved by UHPLC-ESI-MS/MS with the same MS detector. (D. Guillarme). viscosity maintains a reasonable column pressure . Thus, both fast analysis at high linear velocity and enhanced chromatographic resolution with long columns can be easily achieved with SFC. Originally more dedicated to the analysis of lipophilic compounds, modern SFC has also been applied as a powerful technique for the analysis of molecules exhibiting a broad range of polarity including pharmaceuticals , natural products [6], ionic compounds [7], and even more recently peptides [8] thanks in part to the modification of the supercritical CO 2 mobile phase with small amount of polar organic solvents . Using such a binary mobile phase, the technique is still referenced as supercritical fluid chromatography for the sake of simplification even if, above a certain amount of organic modifier, the mobile phase is generally no longer rigorously under supercritical state but rather in a subcritical state. Nevertheless, no phase disruption between these two states is observed on the detected signal and the advantageous mobile phase properties http://dx.
A unified classification of stationary phases for packed column supercritical fluid chromatography
Journal of Chromatography A, 2008
The use of supercritical fluids as chromatographic mobile phases allows to obtain rapid separations with high efficiency on packed columns, which could favour the replacement of numerous HPLC methods by supercritical fluid chromatography (SFC) ones. Moreover, despite some unexpected chromatographic behaviours, general retention rules are now well understood, and mainly depend on the nature of the stationary phase. The use of polar stationary phases improves the retention of polar compounds, when C18-bonded silica favours the retention of hydrocarbonaceous compounds. In this sense, reversed-phase and normal-phase chromatography can be achieved in SFC, as in HPLC. However, these two domains are clearly separated in HPLC due to the opposite polarity of the mobile phases used for each method. In SFC, the same mobile phase can be used with both polar and nonpolar stationary phases. Consequently, the need for a novel classification of stationary phases in SFC appears, allowing a unification of the classical reversed-and normal-phase domains. In this objective, the paper presents the development of a five-dimensional classification based on retention data for 94-111 solutes, using 28 commercially available columns representative of three major types of stationary phases. This classification diagram is based on a linear solvation energy relationship, on the use of solvation vectors and the calculation of similarity factors between the different chromatographic systems. This classification will be of great help in the choice of the well-suited stationary phase, either in regards of a particular separation or to improve the coupling of columns with complementary properties.
Journal of Chromatography A, 2012
All stationary phase chemistries are useful to achiral packed-column supercritical fluid chromatography (pSFC), but the majority of recent applications are based on polar stationary phases of the type used in normal-phase HPLC. Some manufacturers have recently introduced pSFC-tailored stationary phases, while others simply advocate the use of selected HPLC columns among their brands for SFC use. Indeed, any column developed for HPLC use can be used with supercritical fluids. Besides, hydrophilic interaction liquid chromatography (HILIC) is facing an increasing interest. Consequently, a number of HILIC-devoted stationary phases are now commercialized by most column manufacturers. As HILIC stationary phases are polar, their possible use in pSFC seems obvious, although literature examples are not numerous. However, whether they provide acceptable peak shapes in SFC conditions is a serious concern for them to find applicability. Indeed, columns optimized for HILIC mobile phases may not be optimum for SFC mobile phases. We present the characterization of eleven HILIC-type stationary phases used with carbon dioxide-methanol mobile phases in the isocratic mode. The columns are compared in terms of their retention and separation characteristics assessed by the solvation parameter model, and based on peak shapes. For this purpose, hundred and forty-six low molecular weight molecules, comprising neutral, basic and acidic compounds, were eluted on each column. Data analysis is carried out with hierarchical cluster analysis and principal component analysis in order to define three clusters of columns with similar selectivity: the first cluster comprises neutral stationary phases like amide and diol phases; the second one comprises basic stationary phases like aminopropyl-bonded silica; the last cluster comprises bare silica stationary phases. Sample applications with three different test mixtures relevant to pharmaceutical applications (barbiturates, benzodiazepines and propionic acids) are presented to assess the complementarity of some selected columns.