Ezzeldin Essam, Iqbal Muzaffar, Mostafa Gamal, Al-Rashood Khalid A, El-Nahhas Toqa
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Bioavailability Laboratory, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
Biomed Chromatogr. 2018 Mar;32(3). doi: 10.1002/bmc.4131. Epub 2017 Dec 17.
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 C 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.
奎扎替尼是一种高效的类fms酪氨酸激酶受体抑制剂，该受体是急性髓系白血病中最常见的突变基因之一。奎扎替尼在复发/难治性急性髓系白血病患者中显示出显著的抗白血病临床疗效。本研究旨在开发并验证一种使用液相色谱-串联质谱法（LC-MS/MS）测定大鼠血浆中奎扎替尼的分析方法。该方法根据美国食品药品监督管理局的指南进行了验证，本研究获得的结果符合既定标准。采用液-液萃取法，并在BEH C柱上实现色谱分离。使用正离子模式电喷雾电离在多反应监测模式下对奎扎替尼进行检测。分别监测了奎扎替尼和伊布替尼在质荷比（m/z）为561.129/114.09和441.16/84.03时的MS/MS离子跃迁。线性检测范围为2-1000 ng/mL（r>0.998），日内和日间测定精密度分别≤13.07%和13.17%。这种快速、简单且灵敏方法经过验证，并成功应用于大鼠样本中奎扎替尼的药代动力学研究。
