Rolf W. Sparidans

We developed and validated an assay utilizing a liquid chromatography–tandem mass spectrometry technique to quantify the KRAS inhibitor adagrasib in mouse plasma and seven tissue‐related matrices. The straightforward protein precipitation technique was selected to extract adagrasib and the internal standard salinomycin from the matrices. Gradient elution of acetonitrile and water modified with 0.5% (v/v) ammonium hydroxide and 0.02% (v/v) acetic acid on a C 18 column at a flow rate of 0.6 ml/min was applied to separate the analytes. Both adagrasib and salinomycin were detected with a triple quadrupole mass spectrometer with positive electrospray ionization in a selected reaction monitoring mode. A linear calibration range of 2–2,000 ng/ml of adagrasib was demonstrated during the validation. In addition, the reported precision values (intra‐ and inter‐day) were between 3.5 and 14.9%, while the accuracy values were 85.5–111.0% for all tested levels in all investigated matrices. Adagrasib in mouse plasma was reported to have good stability at room temperature, while adagrasib in tissue‐related matrices was stable on ice for up to 4 h (matrix dependent). Finally, this method was successfully applied to determine the pharmacokinetic profile and tissue distribution of adagrasib in wild‐type mice.