Development and validation of an LC-MS/MS method for the quantification of imatinib and imatinib-d8 in human plasma for the support of an absolute bioavailability microdose trial

Here we describe the development and validation of an LC-MS/MS method for the quantification of imatinib and imatinib-d8 in plasma for the support of a clinical absolute bioavailability microdosing trial. The focus lies on the technical aspects to analyse high concentrations of imatinib and low concentrations of imatinib-d8 that are present simultaneously in study samples, using a single sample processing and analytical method. With the validated assay, imatinib and imatinib-d8 can be quantified simultaneously in ranges from 25.0 - 5,000 ng/mL and 0.01 - 2.0 ng/mL, respectively. The method was successfully applied in an imatinib-d8 absolute bioavailability microdosing trial, where a 100 μg imatinib-d8 microdose was intravenously administered to a patient on oral imatinib treatment 400 mg once daily.