Method development for quantification of quizartinib in rat plasma by liquid chromatography/tandem mass spectrometry for pharmacokinetic application. (17th December 2017)

• Record Type: Journal Article
• Authors: Ezzeldin, Essam; Iqbal, Muzaffar; Mostafa, Gamal; Al‐Rashood, Khalid A.; El‐Nahhas, Toqa
• Is Part Of: Biomedical chromatography. Volume 32:Number 3(2018)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-12-17
• Subjects: pharmacokinetic -- plasma -- quizartinib -- UHPLC–MS/MS; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.4131
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: Quizartinib is a highly potent inhibitor of the fms‐like tyrosine kinase receptor, which is one of the most commonly mutated genes in acute myeloid leukemia. Quizartinib has shown a significant antileukemic clinical influence among relapsed/refractory acute myeloid leukemia patients. This study aimed at developing and validating an analytical method for the measurement of quizartinib in rat plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The method was validated according to US Food and Drug Administration guidelines, and the results obtained in this work met the set criteria. Liquid–liquid extraction was used and chromatographic separation was achieved on a BEHTM C18 column. Detection of quizartinib was achieved in multiple reaction monitoring mode using positive‐ion mode electrospray ionization. The MS/MS ion transitions at mass‐to‐charge ratios ( m / z ) of 561.129/114.09 and 441.16/84.03 were monitored for quizartinib and ibrutinib, respectively. The linear detection range was 2–1000 ng/mL ( r > 0.998), with intra‐ and inter‐day assay precisions ≤13.07 and 13.17%, respectively. This rapid, simple and sensitive method was validated and successfully applied to the pharmacokinetic study of quizartinib in rat samples.