Bioanalysis of tucatinib and metabolite, and a five-way cross-validation to support clinical pharmacokinetic analysis

Area of Science:

• Pharmacology and Drug Development
• Analytical Chemistry

Background:

• Tucatinib is a HER2 tyrosine kinase inhibitor used for metastatic cancers.
• Accurate quantification of drug plasma concentrations is crucial for pharmacokinetic analysis in clinical trials.

Purpose of the Study:

• To develop and validate a cross-validation method for tucatinib plasma concentration analysis.
• To enable the combination of data from multiple tucatinib clinical trials for population pharmacokinetic analysis.

Main Methods:

• A five-way cross-validation procedure was established.
• Bioanalysis from one laboratory and method served as the 'base' for validating other methods.
• Mass spectrometry/mass spectrometry (MS/MS) analysis was employed.

Main Results:

• The developed cross-validation method confirmed comparability of tucatinib data across laboratories and methods.
• This approach offers an alternative to multiple head-to-head method comparisons.
• Facilitated the pooling of data from diverse clinical trials.

Conclusions:

• The five-way cross-validation procedure is effective for ensuring data integrity in tucatinib pharmacokinetic studies.
• This method supports robust population pharmacokinetic analysis by enabling data integration.
• Enhances the reliability of drug quantification in multi-laboratory, multi-method settings.