Quantitative bioanalytical assay for the human epidermal growth factor receptor (HER) inhibitor dacomitinib in rat plasma by UPLC-MS/MS
•A method for the analysis of dacomitinib in plasma was developed for first time.•The method produced a linear range of 1–150 ng/mL dacomitinib in rat plasma.•The method was successful at detecting dacomitinib from treated rats. Dacomitinib is a highly selective irreversible small-molecule inhibitor...
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Published in | Journal of pharmaceutical and biomedical analysis Vol. 166; pp. 66 - 70 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
Elsevier B.V
20.03.2019
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Subjects | |
Online Access | Get full text |
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Summary: | •A method for the analysis of dacomitinib in plasma was developed for first time.•The method produced a linear range of 1–150 ng/mL dacomitinib in rat plasma.•The method was successful at detecting dacomitinib from treated rats.
Dacomitinib is a highly selective irreversible small-molecule inhibitor of the human epidermal growth factor receptor (HER) family of tyrosine kinases. A simple and quick bioanalytical method was completely developed and validated for the assay and pharmacokinetic investigation of dacomitinib in rat plasma using ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Proteins in 0.1 mL plasma samples were prepared by precipitant acetonitrile containing ibrutinib as the internal standard (IS). Separation of the analyte from plasma samples was carried out on an Acquity UPLC BEH C18 column using acetonitrile and 0.1% formic acid in water as mobile phase for gradient elution. The total run time and the elution time of dacomitinib were 3.0 min and 1.07 min, respectively. Positive-ion electrospray ionization (ESI) and multiple reaction monitoring (MRM) on a triple quadrupole tandem mass spectrometer were used for detection at the transitions of m/z 470.1 → 124.1 for dacomitinib and m/z 441.2 → 84.3 for ibrutinib (IS), respectively. In the range of 1–150 ng/mL, the calibration curve of dacomitinib was linear with a lower limit of quantitation (LLOQ) of 1 ng/mL. Mean recovery of dacomitinib in plasma was in the range of 76.9–84.1%. The inter- and intra-day precision (RSD) was in the scope of 1.7–8.7% and the accuracy (RE) ranged from -6.1 to 8.5%. Stability studies under different conditions were indicated to be stable. A pharmacokinetic study after oral administration of 40 mg/kg dacomitinib in rats illustrated the applicability of the new presented determination of dacomitinib. |
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ISSN: | 0731-7085 1873-264X |
DOI: | 10.1016/j.jpba.2018.12.041 |