Compound management

This author has not heard any reports at compound management conferences of significant problems initially dissolving compounds in dry DMSO. In the author s experience initial solubilization of compounds in DMSO is seldom a problem. At the author s Pfizer lab over 40 000 compounds were dissolved in DMSO at a 60 mM concentration. Problems dissolving a wide range of structures were so few that they were not worth tracking. However, virtually none of these 40000 compounds dissolved were crystalline. 

Scientists within compound management groups face the challenge to select the best compounds from this huge pool of available chemicals. At AstraZeneca criteria used for compound selection include ... 

Compound management, testing process, and assay and data validation... 

Archer JR (2004) History evolution, and trends in compound management for high throughput screening. ASSAY Drug Dev Technol 2 675-681... 

Quite often the profiling group initiates the activities of compound management and coordinate the preparation of biological material from cell biology. This may require one to three... 

The just in time supply of plates from the compound management and cell biology groups seems to be a more critical operational hurdle. The ADME/Tox screening... 

This is a common approach. A central LIMS system keeps track of the compounds, layout of plates supplied from compound management and the assays requested for each sample. Scientists track the mapping of samples though the preparation of test plates, sample preparation and analysis with the help of macros (usually programmed in Excel). At the conclusion of the experiment, data is uploaded back into the LIMS system for review and delivery to the requesting scientist. 

FIGURE 12.1 Typical compound management processes supporting HTS. Top (gray area) inventory management. Middle compound dispensing and distribution. Bottom (gray area) HTS activities. 

A typical HTS campaign may require hundreds of thousands of samples delivered daily. Thus it is necessary to have all neat (solid) samples in liquid form in order to prepare and deliver them quickly. The first process in compound management to support HTS is dissolution of all solid samples into solutions—a process known as solubilization that makes samples readily available for biological testing. Another advantage to centralized compound solubilization, even for post-HTS activities, is to preserve the samples and reduce waste of the crown jewels. Compound solubilization usually requires (1) selection of solvent, (2) determining concentration and volume, (3) weighing of solids, and (4) solubilization. 

Determining target concentration is important because it must work for most processes after the sample is solubilized to a certain concentration. After solubilization, a lower concentration solution may be achieved by dilution, but it is no longer possible to fill a request for a higher concentration. Therefore, a compound management laboratory must ensure the concentration is high enough to cover the needs of its customers. Further, more solubility issues may arise as the concentration increases. 

Storage conditions represent another challenging aspect of compound management. No single consensus dictates the best way to store and process samples. However, the following major factors are commonly considered when determining storage conditions. 

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