Sample pooling to expedite bioanalysis and pharmacokinetic research

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Bioanalytical Chemistry
• Drug Discovery and Development

Background:

• Pharmacokinetic (PK) characterization is crucial but often limits drug discovery and development throughput.
• High-volume bioanalysis for biodisposition studies presents a significant hurdle in IND and NDA phases.
• Existing cocktail dosing methods raise concerns about drug-drug interactions and other limitations.

Purpose of the Study:

• To investigate sample pooling with one-in-one dosing as an alternative to cocktail dosing for enhancing PK screening throughput.
• To demonstrate the concept and utility of sample pooling in PK screening and characterization.
• To explore innovative bioanalytical approaches for accelerating drug development.

Main Methods:

• Utilized six proprietary dopamine D4 receptor antagonist preleads (C1-C6) as model compounds.
• Administered compounds orally to rats using a one-in-one dosing strategy (one compound per animal).
• Pooled plasma samples from different rats at each time point and performed simultaneous quantitation using HPLC and one-step liquid-liquid extraction.

Main Results:

• Achieved substantial PK information for six preleads simultaneously from pooled samples, significantly reducing workload compared to analyzing compounds individually.
• Demonstrated that sample pooling with one-in-one dosing can enhance throughput in PK screening during the discovery phase.
• Indicated the potential of sample pooling to improve PK characterization throughput in the development phase.

Conclusions:

• Sample pooling combined with one-in-one dosing offers a viable strategy to increase PK screening and characterization throughput in drug discovery and development.
• This approach represents an innovative bioanalytical method that can streamline PK studies.
• The method holds promise for optimizing bioanalytical workflows, especially with advancements in LC-MS technology.