An automated system for the purification of combinatorial libraries by preparative LC/MS

Abstract

The emergence of combinatorial chemistry and parallel synthesis techniques in pharma-

Maximizing Automation in LC/MS High-Throughput Analysis and Purification

“…We have used this procedure for several years now in our lab using Excel macros; however, through the establishment of our new platform, this step has now become fully automated. It is emphasized that the design and the assignment of our optimized preparative gradients results purely from empirical correlations using large sample sets and does not require any common conditions (e.g., slope) for the analytical and preparative runs. ,,, Since the RT is very critical, however, we decided to install our analytical four-channel MUX system with four individual pumps. Other systems utilize only one pump with a subsequent four- or eight-way split, , but we felt the danger of incorrect RTs resulting from columns with different back-pressures to be too high …”

High-Throughput Purification of Combinatorial Arrays

“…Most reports in the literature seem to favor this approach. [13][14][15] Minimal reequilibration was used in all separations. This did not appear to affect chromatographic performance or column lifetime.…”

“…Our experience suggests that it is more practical to have a handful of methods that can be selected on the basis of information obtained on reaction analyses. Most reports in the literature seem to favor this approach. − …”

The Expanding Role of HPLC in Drug Discovery

“…Kibbey [47] was one of the first scientists to implement a fully automated preparative LC/MS system for combinatorial library purification. His approach was to perform a scouting analytical run prior to purification so as to optimize chromatographic method and fraction collection parameters.…”