Validated UPLC-MS/MS method for Determination of Dacomitinib in Rat Plasma and its Application to Pharmacokinetic Study

Dacomitinib is a second-generation irreversible epidermal growth factor receptor tyrosine kinase inhibitor. In this work, a sensitive and selective UPLC-MS/MS method for determination of dacomitinib in rat plasma was developed. Protein precipitation by acetonitrile-methanol (9:1, v/v) was used to prepare samples with the addition of enasidenib as an internal standard (IS). Chromatographic separation was achieved on a CORTECS UPLC C18 column (2.1 x 50 mm, 1.6 mu m) with acetonitrile and water (containing 0.1% formic acid) as the mobile phase with gradient elution at a flow rate of 0.4 mL/min. Multiple reaction monitoring (MRM) mode with the positive electrospray ionization was quantified using target fragment ions m/z 471.21 -> 128.1 for dacomitinb and m/z 474.57 -> 456.64 for IS. Calibration plots were linear through-out the range 1-500 ng/mL for dacomitinb in rat plasma. The standard curves of dacomitinb were linear, and the lower quantification limit was 0.1 ng/mL. Mean recoveries of dacomitinb in rat plasma ranged from 86.1% to 94.8%. RSD of intra-day and inter-day precision were both < 8.59%. The accuracy of the method was between 95.48% to 106.59%. The developed and validated method was perfectly used in the pharmacokinetic study of dacomitinb after gavage administration in rats.

Automated summary

In this study, a sensitive and selective UPLC-MS/MS method for determination of dacomitinib in rat plasma was developed. The method showed good linearity and high recovery rate, which was successfully validated in pharmacokinetic study of dacomitinib in rats.