Evaluating passive permeability
Focused on early discovery, we understand that compounds at this stage often suffer from low aqueous solubility and high non-specific binding. That’s why we don’t assume that compounds are fully-soluble under the assay conditions, nor do we rely on assumed mass balance. Instead, with as little as 20 μL of 10 mM DMSO stock solution, we measure actual dose concentration (Co) along with the concentration in the donor and acceptor wells.
To avoid non-specific binding, we’ve incorporated Corning Gentest™ pre-coated PAMPA plates into our workflow. Unlike traditional PAMPA formulations, these plates are comprised of an oil-lipid-oil tri-layer, offering a shortened path for compound diffusion more closely mimicking diffusion across the cell membrane while minimizing non-specific binding and improving the accuracy of PAMPA permeability values for compounds that are typically under-predicted using traditional PAMPA methods.
In an internal validation study using 24 commercial compounds, the PAMPA assay accurately predicted passive permeability.