Quantitation of capmatinib, a mesenchymal-epithelial transition factor inhibitor by UPLC-MS/MS in rat plasma and its application to a pharmacokinetic study.

Aim: Capmatinib is an orally bioavailable mesenchymal-epithelial transition factor inhibitor with anticancer activity, which has proved preclinical activity in multiple cancer trials. The present study aimed to develop a fast and reliable assay approach to quantify capmatinib in rat plasma. Methodology & results: After protein precipitation with acetonitrile, the chromatographic separation was achieved with an Acquity UPLC BEH C-18 column, and subsequently detected with positive electrospray ionization via a triple quadrupole tandem mass spectrometer. The target quantitative ion pairs m/z 412.99 -> 381.84 for capmatinib and 387.00 -> 355.81 for the internal standard, respectively. The calibration curve for the assay was linear over the range of 1.0-4000 ng/ml. Conclusion: The method shows an excellent performance in linearity, accuracy, precision, stability, and has been successfully applied to a pharmacokinetic study after oral administration of capmatinib at three doses (5, 10 and 20 mg/kg) in rats.