A Novel Method for Preventing Non-specific Binding in Equilibrium Dialysis Assays Using Solutol® as an Additive

Area of Science:

• Pharmacology and Toxicology
• Drug Development
• Bioanalytical Chemistry

Background:

• Accurate determination of plasma unbound fraction is crucial for drug pharmacology, toxicology, pharmacokinetics, and drug-drug interaction prediction.
• Increasingly lipophilic compounds challenge traditional ADME assays due to issues like non-specific binding and low solubility.
• Non-specific binding in assays limits sensitivity and prevents accurate unbound fraction determination for highly bound compounds.

Purpose of the Study:

• To investigate the efficacy of Solutol® as an excipient to mitigate non-specific binding in equilibrium dialysis.
• To assess the impact of Solutol® on the accurate determination of unbound fraction for challenging lipophilic compounds.

Main Methods:

• Equilibrium dialysis assay modified with the addition of 0.01% v/v Solutol®.
• Evaluation of Solutol®'s effect on non-specific binding to dialysis membranes and plasma proteins.
• Testing the method with a set of compounds to compare unbound fraction values.

Main Results:

• Solutol® effectively prevented non-specific binding to the dialysis membrane.
• Solutol® demonstrated no significant non-specific binding to plasma proteins.
• The modified assay yielded comparable unbound fraction values to existing methods for a test set of compounds.

Conclusions:

• Solutol® can be utilized as an additive in equilibrium dialysis to mitigate non-specific binding.
• This approach enables the accurate determination of unbound fraction for highly lipophilic compounds.
• The use of Solutol® enhances the reliability of pharmacokinetic and toxicological assessments for new chemical entities.