Compound management: guidelines for compound storage, provision, and quality control.

The scientific discipline of compound management has developed significantly over the last decade, as witnessed by the large number of conferences dedicated to this topic. The key elements of compound management include (1) the management, storage, and processing of both solids and liquids; (2) compound delivery and interface with key customers; (3) performance of instruments and automation that support these operations; (4) analytical techniques used for quality assurance; and (5) sample informatics, including registration, routing, and compound quality data. This article incorporates guidelines, best practices, and experimental protocols for these key aspects of compound management. Curr. Protoc. Chem. Biol. 3:141-152 © 2011 by John Wiley & Sons, Inc.

Applications of adaptive focused acoustics to compound management.

Since the introduction of lithotripsy kidney stone therapy, Focused Acoustics and its properties have been thoroughly utilized in medicine and exploration. More recently, Compound Management is exploring its applications and benefits to sample integrity. There are 2 forms of Focused Acoustics: Acoustic Droplet Ejection and Adaptive Focused Acoustics, which work by emitting high-powered acoustic waves through water toward a focused point. This focused power results in noncontact plate-to-plate sample transfer or sample dissolution, respectively. For the purposes of this article, only Adaptive Focused Acoustics will be addressed. Adaptive Focused Acoustics uses high-powered acoustic waves to mix, homogenize, dissolve, and thaw samples. It facilitates transferable samples through noncontact, closed-container, isothermal mixing. Experimental results show significantly reduced mixing times, limited degradation, and ideal use for heat-sensitive compounds. Upon implementation, acoustic dissolution has reduced the number of samples requiring longer mixing times as well as reducing the number impacted by incomplete compound dissolution. It has also helped in increasing the overall sample concentration from 6 to 8 mM to 8 to 10 mM by ensuring complete compound solubilization. The application of Adaptive Focused Acoustics, however, cannot be applied to all Compound Management processes, such as sample thawing and low-volume sample reconstitution. This article will go on to describe the areas where Adaptive Focused Acoustics adds value as well as areas in which it has shown no clear benefit.

Stability through the ages: the GSK experience.

It is common knowledge in the pharmaceutical industry that the quality of a company's compound collection has a major influence on the success of biological screening in drug discovery programs. DMSO is the widely accepted solvent of choice for storage of compounds, despite the hygroscopic nature of the solvent, which can lead to stability issues. Other factors that can affect compound stability (e.g., degradation, precipitation) include concentration of compound, intrinsic compound stability, presence of reactive contaminants, storage format-related factors (vessel, sealing, etc.), storage conditions (temperature, humidity, freeze-thaw technique and cycles, etc.), and storage time. To define the best practice for the storage and handling of solution samples, GlaxoSmithKline has undertaken stability experiments over more than a decade, initially to support the implementation of new automated liquid stores (ALS) and, subsequently, to enhance storage and use of compounds in solution through an understanding of compound degradation under storage and assay conditions. The experiments described used a number of technologies, including hyphenated liquid chromatography, electrospray mass spectrometry, flow chemiluminescence nitrogen detection, nuclear magnetic resonance, and Karl Fischer titration.