An original self-assembly using a tetrathiafulvalene-based molecular clip for the recognition of fullerene C.

A glycoluril-based molecular clip incorporating two tetrathiafulvalene (TTF) sidewalls has been synthesized using a straightforward Diels-Alder synthetic route and its ability to self-assemble with fullerene C60 in a 2 : 1 stoichiometry has been demonstrated in solution.

Purification of drug degradation products supported by analytical and preparative supercritical fluid chromatography.

A stressed degradation (oxidation) was employed to produce metabolites from an active pharmaceutical ingredient (API) with large molecular weight (about 900 g/mol). An analytical chromatographic method was desired to compare the products generated by different degradation methods while a multi-gram-scale preparative chromatographic method was necessary to purify the produced metabolites. Supercritical fluid chromatography (SFC) was selected for both tasks as no other chromatographic method had achieved the resolution of the API and metabolites (two isomeric mono-oxide species and one di-oxide).

Unravelling the effects of mobile phase additives in supercritical fluid chromatography-Part II: Adsorption on the stationary phase.

The mobile phases employed in current practice of supercritical fluid chromatography (SFC) are usually composed of a mixture of pressurized carbon dioxide and a co-solvent. The co-solvent is most often an alcohol and may contain a third component in small proportions, called an additive (acid, base or salt). In the first part of this series, the effects of mobile phase additives on the polarity and apparent pH of the mobile phase were explored.

Impurity profiling of drug candidates: Analytical strategies using reversed-phase and mixed-mode high-performance liquid chromatography methods.

The development of new active pharmaceutical ingredients (API) requires accurate impurity profiling. Nowadays, reversed-phase HPLC (RPLC) on C18 stationary phase is the method of first choice for this task and usually employed in generic screening methods. However, this method sometimes fails, especially when the target analyte is not sufficiently retained, making impurity analysis difficult or even impossible.

Interest of achiral-achiral tandem columns for impurity profiling of synthetic drugs with supercritical fluid chromatography.

To achieve the most complete impurity profiling of synthetic drugs with a single chromatographic technique, high resolution is required, which may be gained with a combination of high efficiency and versatile selectivity, allowing to separate most similar analytes. Compared to a single-column chromatographic method, coupling complementary stationary phases promises both an increase in efficiency and an increase in selectivity possibilities. With supercritical fluid chromatography (SFC), the use of long columns is facilitated by the low viscosity of the mobile phase.

Enantioseparation of novel chiral sulfoxides on chlorinated polysaccharide stationary phases in supercritical fluid chromatography.

Asymmetric sulfoxides is a particular case of chirality that may be found in natural as well as synthetic products. Twenty-four original molecules containing a sulfur atom as a centre of chirality were analyzed in supercritical fluid chromatography on seven polysaccharide-based chiral stationary phases (CSP) with carbon dioxide - methanol mobile phases. While all the tested CSP provided enantioseparation for a large part of the racemates, chlorinated cellulosic phases proved to be both highly retentive and highly enantioselective towards these species.

Comparison of ultra-high performance methods in liquid and supercritical fluid chromatography coupled to electrospray ionization - mass spectrometry for impurity profiling of drug candidates.

Impurity profiling of organic products synthesized as possible drug candidates represents a major analytical challenge. Complementary analytical methods are required to ensure that all impurities are detected. Both high-performance liquid chromatography (HPLC) and supercritical fluid chromatography (SFC) can be used for this purpose.

An improved classification of stationary phases for ultra-high performance supercritical fluid chromatography.

Supercritical fluid chromatography (SFC) has recently benefited of new instrumentation, together with the availability of many ultra-high performance columns (sub -2μm fully porous particles or sub -3μm superficially porous particles), rendering it more attractive than ever. Most of these columns commonly used in SFC were initially developed for HPLC use, with an increasing number of stationary phases specifically designed for SFC. While the availability of different stationary phase chemistries is an advantage to achieve successful SFC separations, selecting a column for method development remains difficult.

Use and practice of achiral and chiral supercritical fluid chromatography in pharmaceutical analysis and purification.

The interest of pharmaceutical companies for complementary high-performance chromatographic tools to assess a product's purity or enhance this purity is on the rise. The high-throughput capability and economic benefits of supercritical fluid chromatography, but also the "green" aspect of CO2 as the principal solvent, render supercritical fluid chromatography very attractive for a wide range of pharmaceutical applications. The recent reintroduction of new robust instruments dedicated to supercritical fluid chromatography and the progress in stationary phase technology have also greatly benefited supercritical fluid chromatography.

An attempt to estimate ionic interactions with phenyl and pentafluorophenyl stationary phases in supercritical fluid chromatography.

Pentafluorophenyl-bonded silica (PFP) phases employed in high-performance liquid chromatography (HPLC) often provide very different results depending on the column manufacturer. PFP phases also provide significantly different selectivity from non-fluorinated aromatic phases. As all HPLC columns can also be employed with carbon dioxide-based mobile phases, PFP phases can also be useful to supercritical fluid chromatography (SFC).

Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part II. Selection of an orthogonal set of stationary phases.

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.

Development of an achiral supercritical fluid chromatography method with ultraviolet absorbance and mass spectrometric detection for impurity profiling of drug candidates. Part I: Optimization of mobile phase composition.

Supercritical fluid chromatography (SFC) is a very useful tool in the purpose of impurity profiling of drug candidates, as an adequate selection of stationary phases can provide orthogonal separations so as to maximize the chances to see all impurities. The purpose of the present work is to develop a method for chemical purity assessment. The first part, presented here, focuses on mobile phase selection to ensure adequate elution and detection of drug-like molecules, while the second part focuses on stationary phase selection for optimal separation and orthogonality.