No abstract

The ease of use of the newer liquid chromatography-mass spectrometry interfaces has made possible the automated acquisition of spectra from large batch queues of samples. This fact, combined with the realization that unit molecular mass determination was the only datum desired by a majority of drug discovery synthetic chemists, led us to develop open access mass spectrometry in the early 1990s. Open access spectrometers now scan over 100,000 samples per year from synthesis laboratories at Pfizer. Our experiences with this novel use of mass spectrometry in a large research facility are discussed and we detail some of the pitfalls we believe to be common to this approach. In addition, we offer some reflection on the cultural changes we have observed in our research environment since this experiment began.

Extensive automation of both random and rational drug discovery strategies greatly increases the number of compounds entering biological screens. Although parallel synthesis (one compound per well) strategies eliminate the deconvolution step necessary when pooled libraries are screened, parallel synthesis products are usually screened as crude mixtures, because purification slows the process of lead discovery. Screening crude products is sometimes complicated by synergies and interferences between compounds. Screening pure compounds is the only sure route to immediate, reliable structure -activity relationships.Automated purification strategies are designed to limit or remove the purification bottleneck between synthesis and screening. In this paper, a workstation is described which uses a combination of UV absorbance and mass spectrometric data to make real-time decisions for HPLC fraction collection, allowing selection of compounds based on mass or substructure. This methodology has demonstrated success with parallel synthesis products in drug discovery applications. #

No abstract

No abstract