Liquid chromatography-tandem mass spectrometric assay for ponatinib and N-desmethyl ponatinib in mouse plasma

The linear assay was validated in the ranges 5-5000 ng/ml for ponatinib and 1-1000 ng/ml for N-desmethyl ponatinib. Within-run (n = 18) and between-run (3 runs; n = 18) precisions were 10% and 12% at the lower limit of quantification for the metabolite, all other precisions were ≤8% for the metabolite and ≤6% for ponatinib. Accuracies were between 92 and 108% for both compounds in the whole calibration range. The drug was sufficiently stable under most relevant analytical conditions, only ponatinib showed more than 15% hydrolytic degradation after storage for 6 h and longer at ambient temperature in mouse plasma. Finally, the assay was successfully applied to determine plasma drug levels and study pharmacokinetics after oral administration of ponatinib to female FVB mice.