Solubility Screening Measurements at Organon Newhouse. Darren Edwards Organon Laboratories, Newhouse. Outline. Brief introduction to Organon Newhouse Requirements for a solubility screen How we screen for solubility – SolKin Validation of SolKin Description of what was done
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Organon Laboratories, Newhouse
Lead Finding Teams
Proof of Concept Teams
Pre-clinical / CMC
Pre-clinical / CMC
Physchem assays in support of HO and LO projects
Mix 24 hoursin 96-well plate
Filter (Millipore PCTE)
1:10 dilution with DMSO
1:20 dilution with DMSO
Inject 3 different volumes(4, 8, 12 µl) to give calibration curveSchematic of SolKin method
Inject two different volumes(5 and 50 µl) and quantify
All done in two 96-well platesOne for samples, one for standards
Agilent 1100 system
WATER + 0.1% Formic acid
+ 0.1% Formic acid
HPLC column, 5 cm Xterra C18, 3.5 µm
Dionex Chromeleon and Excel
Is this comparison useful?
How good is literature data?
Highlights lack of published data
2% DMSO – upper limit for MW 500 = 100 mg/l
5% DMSO – upper limit for MW 500 = 250 mg/l
2% DMSO chosen100 mg/l upper limit considered acceptableLimited dataset!
Results after 1.5 hours consistently higher than those after 24 hours agitation. 24 hours gives better correlation to literature.Chose 24 hours, but 1.5 hours OK for screen?
Using data to try and generate acceptance criteria for assay and give idea of variability
Variation can be detected and data rejected if necessary.
Special cause – 9 points below mean
Organon Labs, Newhouse
George Gettinby, Professor of Statistics