Determining compound solubility has become an essential tool in the early stages of the drug discovery process. Low solubility can lead to unreliable results during in-vitro testing. Also, insoluble precipitates have been shown to cause false positives in bioassays, wasting valuable time and resources. Such issues will typically add significant cost to drug research projects. In addition to these factors, the standard shake-flask method used to evaluate drug solubility is inherently low throughput and labor intensive.

Here we describe an automated method for determining drug solubility using Millipore’s MultiScreen Solubility plate on the Biomek® FX workstation. The procedure requires minimal manual intervention by utilizing the gripper for all plate movements on the deck, but shaking occurred offline. It takes about 1 hour and 45 minutes to process on plate of 96 samples (this includes 90 minute shaking off-line). Eight compounds were tested in nine replicates and the results were compared to those achieved through the manual method to demonstrate the viability of the automated protocol. For quantification of aqueous solubility, it is recommended that a standard calibration curve be completed and analyzed for each compound prior to determining aqueous solubility (refer to protocol note PC2445EN00).