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Protein binding and blood partitioning

Fraction unbound and drug distribution

Unbound drug concentration is the major driver of in vitro and in vivo efficacy of drug candidates. Determining the unbound fraction of a drug in plasma, tissue homogenates or assay medium is essential from early to late-stage drug development. Our extensive experience in in vitro distribution studies helps ensure high-quality data you can rely on.

A scientist uses a multifiller to dispense liquid into a rack of vials in a laboratory setting.

Protein binding

Plasma protein binding is crucial for understanding the pharmacokinetic behavior and pharmacological/toxicological effects of a drug. The binding of drug candidates in plasma from various species, or to isolated proteins such as human serum albumin or α-acid-glycoprotein, is determined by equilibrium dialysis or ultracentrifugation. Our in vitro assay may include an investigation of concentration dependency in binding across all matrices.

PPB for new chemical modalities: EScalate assay

In 2024, we implemented the EScalate plasma protein binding (PPB) assay into our services offering. This advanced assay provides highly accurate measurements of plasma protein binding, particularly for compounds with strong binding characteristics. Using a sophisticated microtiter plate system with HSA-coated beads and LC-MS quantification, the EScalate assay overcomes limitations of traditional methods, helping ensure reliable data even for challenging molecules. This enhancement allows us to offer precise and robust data for drug development, supporting our clients in optimizing therapeutic strategies and making informed decisions across multiple species.

Blood partitioning

The concentration ratio of drugs in whole blood versus plasma indicates drug binding to erythrocytes. This is important when comparing clearance estimates directly with organ blood flow rates, such as in the liver, to determine the organ clearance extraction ratio. Our whole blood distribution assay determines the blood-to-plasma ratio for scaling purposes (IVIVE) and estimating hepatic first-pass extraction by converting plasma into blood clearances. These data guide the selection of the most appropriate matrix for pharmacokinetic in vivo studies. Both in vitro distribution studies can be conducted with either radiolabelled or unlabelled test compounds, using liquid scintillation counting or tandem mass spectrometry for quantification, respectively.

 
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