Solubility is a very important physicochemical parameter of a compound.  In bioanalysis in drug discovery and development, solubility has a major impact on bioassays, formulation for in vivo dosing, and intestinal absorption.

The solubility test for organic compounds depends on their structure and solution conditions. Structure determines the lipophilicity, hydrogen bonding, molecular volume, crystal energy and ionizability, which determine solubility. Solution conditions are affected by pH, co-solvents, additives, ionic strength, time and temperature. A good criteria for the solubility of drug discovery compounds is >60 ug/mL.

Solubility Test Method

Kinetic solubility assays are performed in high throughput with shorter incubation times and high throughput analyses using plate readers. The most frequently used of these are the nephelometric assay and direct UV assay, which begin by adding a small volume of DMSO stock solution of each test compound to buffer. In nephelometry, this solution is serially diluted across a microtiter plate and undissolved particles are detected via light scattering. In direct UV, undissolved particles are separated by filtration, after which the dissolved material is quantitated using UV absorption.

Equilibrium solubility assays can be conducted in moderate throughput, by incubating excess solid with buffer and agitating for several days, prior to filtration and HPLC quantitation or LCMS/MS quantification.

Equilibrium solubility is useful for pre-formulation. Kinetic solubility is useful for rapid compound assessment, guiding optimization via structure modification, and diagnosing bioassays. It is useful to customize solubility experiments for compound selection and vehicle development for pharmacology and PK studies.

Solubility Assay Protocol

Compound needed 2-3mg
Stock Concentration 10mg/mL in DMSO(if insoluble or poorly soluble in DMSO,lower concentrations will be used)
Test Conditions pH 7.4,FassIF (pH 6.5),FeSSIF (pH 5.0)SGF (pH 1.2)
Incubation temperature 37°C
Incubation duration 2h
Analysis method LC-MS/MS
Data delivery solubility(mg/mL)
Turn Around Time 5-10 business days

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