Quantitative bioanalytical assay for the human epidermal growth factor receptor (HER) inhibitor dacomitinib in rat plasma by UPLC-MS/MS

Publication date: Available online 28 December 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Xiangjun Qiu, Qianmeng Lin, Zongdi Ning, Xin Qian, Pengbo Li, Lei Ye, Saili XieAbstractDacomitinib 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 standars (IS). Separation of the analyte from plasma samples were 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- a...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research