Ted Szczerba

Successful therapeutic intervention often requires chiral medicines because of the intrinsic chirality of protein drug targets, which consist of L-amino acids. Potency, efficacy, and safety can be highly dependent on the precise stereochemical geometry of the molecules. Determining the biological profile of individual enantiomers in the early stages of drug discovery is important for successful optimization towards clinical candidates. Here we demonstrate the benefits of supercritical fluid chromatography (SFC) with three chiral stationary phases exemplified by high frequency resolution of 41 out of 50 chiral derivatives of eight commonly used drug discovery scaffolds including 1,3-thiazoles, 1,3-benzothiazoles, pyranoquinolones, indoles, and leucolines.

In new drug development, the number of diverse chiral compounds is increasing and sensitive chiral methods are often needed quickly. Many new CSPs are available on the market making it challenging to select the most important ones for the initial screening stages and expedite method development. The focus of this study is to evaluate high selectivity CSPs and to suggest the best screening method with a limited number of high success rate chiral columns.

Chiral chromatography has a wide range of applications in the food, biochemical, and pharmaceutical industries.

Regis Technologies, Inc.

Typical chiral stationary phase (CSP) screening paradigms utilize a single alcohol component as co-solvent in its mobile phase. Recent unexpected observations have demonstrated that mixed-alcohol mobile phases can enhance or even introduce peak resolution when none existed in a mono-alcohol system.

As the number of chiral columns and chiral separations has grown, it has become difficult to organize the information for use in developing new methods. The success of chiral method development depends on the introduction of appropriate columns. The RegisPack? polysaccharide-based chiral stationary phase (CSP) is most successful in achieving a majority of chiral separations. However, there are cases in which this proven chiral selector leads to partial or no separation. Excellent separations using the newly introduced RegisPack? CLA-1 CSP have been obtained for a range of compounds, either by improving or complementing RegisPack's selectivity.

The Pirkle - Type Whelk-O®1 CSP is a synthetically made chiral selector covalently bonded to a silica support. This phase is well known in the industry for its broad degree of generality, mobile phase compatibility, and ability to invert elution order. Most commonly used polysaccharide coated CSP's are sensitive to the presence of certain mobile phase modifiers such as DEA, TEA, and TFA. Retained memory effects can adversely affect a separation resulting in broad and tailing peaks, no peak elution, and reduced or loss of separation altogether. To remove these unwanted memory effects, the column must be rinsed with an alcohol, such as methanol or ethanol. This is a time consuming and costly process. The Whelk-O®1 CSP does not exhibit any such retained memory behavior.

Supercritical Fluid Chromatography (SFC) is quickly becoming a popular choice by chromatographers for analytical and preparative separations.

Supercritical Fluid Chromatography (SFC) is quickly becoming a popular choice by chromatographers for analytical and preparative separations.