HTC-15 - Abstract

Abstract Title: Fast, efficient and selective: separation science for modern organic synthetic chemistry
Abstract Type: Seminar
Session Choice: High Throughput versus High Efficiency Separations (CS)
Presenter Name: Mr Tomas Leek
Co-authors:Mr Johan Soderlund
Dr Peter Sjo
Dr Werngard Czechtizky
Company/Organisation: AstraZeneca
Country: Sweden

Abstract Information :

Within modern drug discovery there is a growing interest to explore compound classes that do not necessary fall within the traditional property space for orally absorbable drugs.

The extended property space and the increased molecular complexity presents additional challenges related to drug discovery including the demands on development of innovative drug formulations and delivery systems for non-oral routes of administration. From a synthetic chemistry perspective each of the individual compound classes possesses a significant challenge regarding synthesis, analysis and purification preceding biological testing.

Although the workhorse for small molecule separations has been reversed-phase (RP) separations with MS detection, a plethora of methods and separation techniques are required to cover the need of compound analysis in the extended property space. Further, the need of both high throughput and high efficiency separations are evident to meet the demands on analytical services during different phases of drug discovery.

With the recent development of analytical Supercritical Fluid Chromatography (SFC) a new route to fast and efficient analysis has emerged. Based on comprehensive method development, we now have a SFC methods designed to meet the analytical needs of a drug discovery project also beyond the traditional drug property space. The SFC methods are both providing orthogonal selectivity towards reversed phase separations and an extend application range. This utility leads to the possibility of replace reversed-phase, hydrophilic interaction chromatography (HILIC) and even some ion-pairing chromatography (IPC) LC systems with a single SFC/MS system.

This presentation will highlight the impact of not only fast and/or highly efficient separations but also the value of utilising orthogonal separation methods. From a performance perspective, the utilisation of sub-2 µ stationary phases and ultrahigh performance instrument in both RP and SFC gives the flexibility to utilise rapid and/or high efficiency separations. The impact of separation science related to organic synthetic chemistry will be illustrated with examples from a) high throughput examples (suitable for monitoring) and b) examples of closely related compounds where a combination of high efficiency and orthogonal selectivity is required for comprehensive chemical analysis prior to biological testing.