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

Tucatinib, a tyrosine kinase inhibitor of HER2, is approved in multiple regions for metastatic breast
cancer and is being evaluated in metastatic colorectal and gastric cancers. During clinical development,
quantification of tucatinib plasma concentrations for pharmacokinetic analysis was performed using
MS/MS analysis by three laboratories using five different methods. Cross-validation was required to
confirm data across laboratories were comparable. A five-way cross-validation procedure was developed
where bioanalysis performed by one laboratory and method was used as a ‘base’ against which the other
methods were validated. This cross-validation method provides an alternative to multiple head-to-head
comparisons between two methods, and enabled combination of data from multiple tucatinib clinical
trials for a single population pharmacokinetic analysis.