Abstract

MS Triggered Fraction Collection on Multi Hundred Gramm Scale

Luigi La Vecchia, Director, Novartis Institutes for BioMedical Research

Silica gel chromatography is a key technology for the purification of intermediates during the chemical synthesis on larger scale. However, still today it is considered to be a bottle neck and it absorbs significant amount of time for its completion. For example in the past we calculated for our planning up to five working days in average to accomplish a purification step in amounts between 250-500 grams of crude material. As a consequence purification of larger amounts of crude chemical compounds has been identified in many pharmaceutical companies to have a high potential for time savings and to speed up the drug discovery process. This is especially the case at the interface of Research and Development where time to deliver is key. Having these time savings in mind, the laboratories of Global Discovery Chemistry Synthesis and Technologies of the Novartis Institute of BioMedical Research Basel have been the first in introducing MS triggered fraction collection at elution rates as high as 1 liter per minute thereby achieving purifications on multi hundred grams. Concurrently with the online MS monitoring, also the exponential gradient elution methodology was established. These two innovations eventually allowed to reduce the time required for larger scale chromatography dramatically. The presentation will also show various examples exemplifying the impact of MS triggered fraction collection at high elution rate and how this changed the way of chromatographic purifications within the working environment.