Characterization of Short-Term Temperature, Exposure, and Solubilization Effects on Library Compound Quality

Abstract

IntroductIon Multiple groups have recognized that maintaining compound quality is dependent on both storage conditions and sample handling methods.1-3 Our workflows within Amgen have been built around low-volume, single-use operational tubes that are periodically prepared as replicates from high-volume, multiuse archive tubes, both stored at temperatures of -8 or -20 °C. This design minimizes the number of times an archive tube must be accessed by instead relying on the single-use tubes for normal operations. This approach effectively serves the majority of the collection, but we have recently noticed that certain compounds enter stages of high demand for a shortened period (<3 months) of time. These high-demand compounds often require frequent replenishment from multiuse archive tubes, which can affect the number of freeze-thaw cycles a compound undergoes. The extended sample handling time can lead to a decrease in overall order fulfillment efficiency and degradation in sample quality from unnecessary exposure outside of the store. Although one potential solution might be to prepare more initial single-use tubes, it is often hard to predict how much material will be required, and the preferred approach has been to replenish on-demand.One alternative approach is short-term storage at room temperature, which would eliminate the need for thawing and reduce sample handling time. Other groups have shown that compound quality can remain stable for 4 to 6 months 4-6 at room temperature, but the labware was significantly different from our archive operations, leading to questions around the form factor used to store compounds. In this study, we wanted to understand the impact of short-term storage at room temperature as compared to the effect of multiple freeze-thaw cycles on overall compound quality in labware relevant to our operations. For our characterization of freeze-thaw events, we were primarily interested in the cumulative effect of both the freeze-thaw and the water uptake that is common with sample handling during formatting Many compound collections are stored under the same temperature conditions, which can limit flexibility by increasing the processing time required for high-demand compounds. In this study, the authors wanted to evaluate the impact of a hybridstorage approach where high-demand compounds are stored for a shortened time period at room temperature to expedite processing operations. The use of a Covaris adaptive-focused acoustics platform was also characterized as a potential enhancement or alternative to storage at elevated temperatures. This study evaluated the impact of temperature, exposure, and solubilization on overall compound quality for short-term storage. A small library of 25 representative compounds was evaluated over an 18-week period to monitor the change in purity and concentration by high-performance liquid chromatography with ultraviolet detection. The authors concluded that temperature had a significant impact on compound concentration, and the effects due to exposure cycles...

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“…The water content of storage mixtures, the temperature, the storage duration, the light expo-sure, the gas under which compounds are placed, and the number of freeze-thaw cycles to which the compounds are subjected are factors that can affect the rate of compound decay. Decay is typically measured through biophysical means, such as NMR and MS (44,45). Less well-known is the rate of compound decay into active breakdown products, a process that is difficult to study because activity can only be defined in the context of a screen target.…”