HTC-15 - Abstract

Abstract Information :

During API (active pharmaceutical ingredient) development, drug stereoisomerism is recognized as an issue having clinical and regulatory implications. Enantiomers have essentially identical physical and chemical properties, while potentially showing large differences in toxicity. Therefore, the stereoisomeric composition of a drug with a chiral center should be well documented. To evaluate the pharmacokinetics of a single enantiomer or any mixture of enantiomers, manufacturers must develop quantitative assays for individual enantiomers early in drug development.

But what technique do we choose, what will we compromise? Obtaining the best choice, the most selectivity surely requires compromise?Chromatography has recently developed a new quality, it now offers more, by being both more selective and more flexible. A new class of hybrid SFC-LC switching systems enables chromatographers to utilise both, the selectivity of liquid chromatography as well as supercritical fluid chromatography with only one system, allowing more complex achiral and chiral separations. Switching from SFC to LC is a seamless and automated process and method screening using both techniques was performed in one overnight sequence.

Fast and simple SFC and LC methods for the separation of chiral compounds were developed within two days, using a column screening system with 6 LC and 6 SFC columns and 3 different organic modifiers for each technique. SFC and LC switching was shown to be a reliable, robust and simple alternative to routine LC screening. Use of the system in terms of complexity of the instrument and method development was very similar to the HPLC approach. However, since SFC is known to be often superior to HPLC for chiral separations, screening with both techniques has proven advantageous.