How to Overcome the Challenges of Nonspecific Binding?

Nonspecific binding is a form of adsorption resulting from noncovalent bonding forces. The phenomenon of adsorption may affect some processes of the whole pharmacokinetic (PK) assays, such as affecting the concentration accuracy of formulation and sample. This blog discusses the common approaches and ideas for solving adsorption problems based on the principles of nonspecific binding occurrence and assay experience.

What are the Common Strategies for Addressing Nonspecific Binding?

The quantity and strength of adsorption of test articles are mainly determined by three factors: (1) the solid surface in contact with the solution, (2) the composition of the solution, (3) and the property of the analyte. In addition to these three factors, some other factors such as ambient temperature, solution pH, and even the number of freeze–thaws the solution undergoes may impact the degree of adsorption, which needs to be examined during the actual assay process.

Therefore, it is crucial to learn the common strategies fornonspecific binding issues:

1. It is first need to know that desorption agents could play a vital role in the desorption of different biological matrices. For instance, adding the organic reagents in the small-volume matrix samples is conducive to increasing the solubility of analytes.

2. Secondly, the addition of surfactants can lead to a more uniform dispersion of analytes in the solution, thereby improving the dissolution state and weakening the hydrophobic effects that produce nonspecific adsorption. ¹

3. In addition to adding desorption agents, the adsorption effect can also be mitigated by using low-adsorption consumables, such as low-adsorption 96-well plates.

What are the Strategies for the Nonspecific Binding of New Modality Drugs?

For new modalities, such as peptides, proteins, and PDC drugs, adjusting the pH of the dissolution solvent. Besides, optimizing the type and composition of the dissolution solvent could improve the compound solubility, and finally reduce the adsorption effect. Meanwhile, careful selection and optimization of desorption agents are crucial to meeting the sensitivity requirements.

Nonspecific binding of compounds may affect the accuracy of pharmacokinetic assay results. Therefore, it is essential to know about the strategies for nonspecific binding.

If you want to learn more details about the strategies for nonspecific binding, please read the article now.

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