A novel, sensitive, and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of Capmatinib in human plasma and its pharmacokinetic application in rabbits. Chromatographic separation of the Capmatinib and internal standard ([13CD3]Capmatinib) were achieved on Phenomenex Luna C18 column (50 mm × 2 mm × 5 μm) with 0.5 ml/minute flow rate and coupled with API6000 triple quadrupole MS in multi reaction monitoring mode by applying mass transitions m/z 413.15–128.05 for Capmatinib and m/z 416.20–131.01 for the internal standard. The calibration curve exhibited linearity over the concentration of 1.0–28,000.0 ng/ml for Capmatinib. The LLOQ was 1.0 ng/ml. The validated LC-MS/MS method was effectively applied for the analysis of plasma in healthy rabbits for the determination of Capmatinib. From pharmacokinetic studies, Capmatinib showed an average AUClast of 12,964.14 ± 635.97 hour*ng/ml and Cmax of 2,537.94 ± 12.42 ng/ml in the subjects. In summary, the developed method has been successfully validated and pharmacokinetic parameters were demonstrated after oral administration of Capmatinib to healthy rabbits.
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