Kozikowski Barbara A, Burt Thomas M, Tirey Debra A, Williams Lisa E, Kuzmak Barbara R, Stanton David T, Morand Kenneth L, Nelson Sandra L
Proctor & Gamble Pharmaceuticals, 8700 Mason Montgomery Road, Mason, OH 45040-8006, USA.
J Biomol Screen. 2003 Apr;8(2):210-5. doi: 10.1177/1087057103252618.
A diverse set of 320 compounds from the Procter & Gamble Pharmaceuticals organic compound repository was prepared as 20-mM DMSO solutions and stored at 4 degrees C under argon in pressurized canisters to simulate a low-humidity environment. The plates were subjected to 25 freeze/thaw cycles while being exposed to ambient atmospheric conditions after each thaw to simulate the time and manner by which compound plates are exposed to the atmosphere during typical liquid-handling and high-throughput screening processes. High-performance liquid chromatography-mass spectrometry with evaporative light-scattering detection was used to quantitate the amount of compound remaining after every 5th freeze/thaw cycle. Control plates were stored either at room temperature under argon or at 4 degrees C under argon without freeze/thaw cycling and were evaluated at the midpoint and the endpoint of the study. The study was conducted over a short time period (i.e., 7 weeks) to minimize the effect of compound degradation over time due to the exposure of the compounds to DMSO. The results from this study will be used to determine the maximum number of freeze/thaw cycles that can be achieved while maintaining acceptable compound integrity.
从宝洁制药有机化合物库中选取了一组多样的320种化合物，制备成20 mM的二甲基亚砜（DMSO）溶液，并在氩气环境下于4摄氏度储存于加压罐中，以模拟低湿度环境。这些平板经过25次冻融循环，每次解冻后暴露于环境大气条件下，以模拟化合物平板在典型的液体处理和高通量筛选过程中暴露于大气的时间和方式。采用带蒸发光散射检测的高效液相色谱 - 质谱联用技术对每第5次冻融循环后剩余的化合物量进行定量。对照平板要么在氩气环境下室温储存，要么在氩气环境下4摄氏度储存且不进行冻融循环，并在研究的中点和终点进行评估。该研究在短时间内（即7周）进行，以尽量减少由于化合物暴露于DMSO而随时间发生降解的影响。本研究的结果将用于确定在保持可接受的化合物完整性的同时能够实现的最大冻融循环次数。
