Dr Brian Freer looks at a new range of immobilised Chiral columns.
Chiral analysis in pharmaceutical laboratories has evolved into a mainstream analytical activity. Automated chiral screening of the four gold columns from Daicel (AD; OD; AS and OJ) in normal and polar organic mobile phases results in a chiral analysis success rate of over 90 per cent.
Daicel has recently introduced two new products – immobilised polysaccharides (CHIRALPAK IA and IB). But where should these columns be used? As an overlap with the current Daicel products to achieve a 100 per cent chiral analytical method development? As stand alone products for low solubility compounds? Used with new solvents for difficult separations? In practice the columns can be used in all of the above modes.
The immobilised products from Daicel consist of silica to which a derivatised polysaccharide polymer has been covalently bonded. This allows the immobilised columns to be used with any miscible chromatographic solvent combination. The current coated Daicel phases must be used solely with permitted mobile phase combinations that do not dissolve the polymer.
The use of any miscible chromatographic solvent mixture provides several enhancements for both analytical and preparative chromatography.
For pharmaceutical compounds, with low solubility in normal and polar organic solvents, the combination of the Daicel polysaccharide selectors and immobilisation ensures a highly loadable separation with good solubility and good resolution, which combine to give excellent productivity. Significant productivity improvements have been found by tailoring the separation to the solvent system that maximises solubility and resolution.
For analytical method development it is currently believed that the mechanism of chiral recognition is affected by interactions between the derivatised polymer and the enantiomer.
A second variable is steric fitting of the enantiomers between the helices of the polymer. The polymers conformation is modified by swelling in the mobile phase. Hence the ability to use a wider variety of solvents permits the polymer structure to be varied significantly and hence a wider range of separations made possible. This has been demonstrated by many laboratories where the immobilised phases have now become a staple for both primary and extended screening of any chiral molecule. The addition of a screening system on the immobilised phases, in combination with an initial screen on the normal and polar organic mode, has resulted in analytical method development success rates of 98 to 100percent.
Users have also noted other benefits of the immobilised columns. Firstly the robustness of the columns to any solvents has allowed some users to consider the use of chiral chromatography in an ‘open access’ environment. Secondly the regeneration technique ensures high separation reproducibility regardless of column history and so allows easy problem solving.
Since their introduction the Daicel immobilised phases have become established in many pharmaceutical laboratories. They are now routinely used alongside CHIRALPAK AS and CHIRALCEL OJ as part of the initial screen in polar organic and normal phase. They are also being widely used in an extended screen for any unresolved samples by using the extended range of solvents. Finally they are used in preparative laboratories due to the ability to tailor a separation to give the highest productivity.
Dr Brian Freer is Business Development Manager, Chiral Technologies Europe, Illkirch, France. www.chiral.fr
