Stability in aqueous solutions is a fundamental requirement to a successful drug candidate. Degradation may be caused by a variety of mechanisms: hydrolysis, oxidation, light-catalysed degradation and others. At early stages of drug discovery, screening for stability in buffer solutions at acidic, neutral and basic pH is desirable for eliminating potentially troublesome candidates.
Chemical stability analyses are often performed by HPLC with UV-Vis detection at 3 wavelengths. Yet, in some cases degradation products may be poorly separated from parent compounds, causing inaccuracy in analysis. For this reason in our lab this analysis is typically performed using LC/MS (although UV-Vis detection can also be performed upon request).
The assay is performed in a reusable 96-well Teflon plate (Millipore) to avoid possible artifacts caused by adsorption of certain compounds to polypropylene surfaces. Upon request, polypropylene plates can be used in the same assay setup for the non-specific binding assessment, which can be conveniently combined with the chemical stability assay, as PTFE (Teflon®) and polypropylene have different binding characteristics.
Deliverable: Stability is calculated as % test compound remaining relative to the T=0 peak area. Full study report is provided.
Sample Submission: A minimal accurately weighable quantity of dry compound (~1 mg or 2 µmol) or 50 µL of 10-20 mM stock DMSO solution is required for this assay. For multiple assays, lesser amount of compound per assay may be sufficient, depending on the particular project. We do not need to know structures of the molecules for ADME testing. However, brutto formulas have to be provided for all studies involving MS detection.