Within the pharmaceutical industry early drug discovery programs are driven by screening experiments that reduce in number as they increase in complexity. As these experiments move from hundreds of thousands of compounds down to tens of compounds, certain conditions remain the same - the compounds themselves are dissolved in di-methyl sulfoxide (DMSO) and this solution is diluted down in aqueous buffers in order that DMSO does not impact the biological system being tested. Whilst a great deal of work has been done looking at the effects of long term storage on screening compounds, there is an assumption that the short time spent between dispense and read-out in an assay has little impact on the sample quality. The aim of this study is to investigate a process that gives early warning of compound assay suitability and thus helps mitigate against false positive/negative assay readout.
We show data from simple buffer-diluted sample sets that highlight the impact of the dispense/readout lag time on the free concentration of the target compound in an assay well, together with examples where the structural stability of the compound is compromised by this short exposure to an aqueous environment.