Application of a Dried-DMSO rapid throughput 24-h equilibrium solubility in advancing discovery candidates.
A rapid throughput equilibrium solubility measurement is described. The method utilizes central liquid storage where compounds are stored as 10mM solution in dimethyl sulfoxide (DMSO). The DMSO is subsequently removed to generate solid like material used for solubility measurement. A full range of available technologies is used including automated liquid handling, automated data collection using both HPLC/UV and LC/MS/MS. The method is fully validated and has been used to measure solubility for over 20,000 compounds across all phases of drug discovery. A detailed discussion on data interpretation and comparison to traditional solubility measurement using solid material is presented. An in-house solubility predictive model has been developed from the vast data set and has been employed successfully as part of compound design resulting in over 30% reduction in the number of poorly soluble compound synthesized.
Alelyunas
Yun W
YW
CNS Chemistry and DMPK Department, AstraZeneca Pharmaceuticals LP, 1800 Concord Pike, P.O. Box 15437, Wilmington, DE 19850-5437, USA. yun.alelyunas@astrazeneca.com
Liu
Ruifeng
R
Pelosi-Kilby
Luciana
L
Shen
Cindy
C
D002851:Chromatography, High Pressure Liquid; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D055808:Drug Discovery; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D053719:Tandem Mass Spectrometry
D004121:Dimethyl Sulfoxide