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Thermodynamic Solubility

Low solubility can be a major obstacle during drug discovery and development, as low solubility can impact the generation of quality in vitro DMPK or biology data, can cause issues in the generation of an appropriate formulation for in vivo pharmacokinetic studies or can cause issues with drug absorption following oral dosing in vivo. If the solubility is known, then solutions can easily be made to the correct concentrations.

The thermodynamic solubility assay is usually a late discovery screening assay that calculates the equilibrium solubility of a test compound by measuring its concentration in a solution containing excess compound which has been allowed to reach thermodynamic equilibrium.

For most test compounds, a solubility of >100 µM is sufficient to determine high solubility. This assay returns results up to 200 µM. Haloperidol is used as a positive control compound.


Compound requirements Solid compounds, two weighings, one of 1-2mg for standard curve and the other 2-3mg for sample
Buffer and pH Phosphate buffered saline at pH7.4
Test Article Concentrations 7 point curve from 0.5 to 200 µM
Replicates Six
Incubation Time 24hr at 25°C under shaking conditions
Analysis Method UPLC-MS/MS
Controls Haloperidol
Data Delivery Equilibrium solubility (µM)




Figure 1 Example of a set of 3 compounds solubility measurements using Sygnature’s Thermodynamic Solubility method. The error bars represent the standard deviations of 6 replicates.


About Us


The DMPK & Physical Sciences department at Sygnature Discovery is dedicated to understanding and optimising the absorption, distribution, metabolism and excretion of drug candidates by working in close partnership with clients and other departments within Sygnature to provide successful optimisation strategies.

We have extensive know-how and expertise to provide well validated, state-of-the-art assays and a comprehensive applied consultancy service for interpretation of the in vitro ADME and in vivo PK data.

Our corporate vision is to accelerate the discovery of new medicines, from the laboratory into development to treat patients.

Our DMPK mission is to deliver tailored DMPK expertise through innovation, quality and commitment.

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