ANYL 55 |
| To meet the challenge of providing physicochemical properties for all lead optimization compounds, a high throughput physicochemical profiling method was developed based on high speed HPLC measurement. The compounds are delivered in the form of DMSO solutions from the same stock solutions for other assays to streamline the compound management. Parallel sample preparation with 96-well plate configuration and multi-channel pipetting are used in the shake-flask solubility assay, shake-flask LogD assay and PAMPA, each at a variety of pH conditions. This profiling assay panel results in 11 quantitative LC analyses for each compound. A fast HPLC method with 2 min gradient analysis, 2.5 min cycle time is used to ensure that all samples are analyzed after an over-night HPLC run. The retention time and peak area of the samples are identified, retrieved and exported by a custom add-on processing method in Waters Empower2. The data are then processed by both a BASIC program and Excel template to calculate the final results. By using the parallel sample preparation, fast HPLC and automatic data processing, up to 96 compounds can be readily profiled in less than 5 days by one person with one HPLC. These physicochemical properties measured help with prioritizing compounds early in the lead optimization period, again later with formulating compounds for in vivo assays. |
|
General Posters
7:00 PM-9:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Division of Analytical Chemistry |