Attwa Mohamed W, Kadi Adnan A, Darwish Hany W, Amer Sawsan M, Alrabiah Haitham
1 Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia.
2 Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
Eur J Mass Spectrom (Chichester). 2018 Aug;24(4):344-351. doi: 10.1177/1469066718768327. Epub 2018 Apr 8.
Foretinib (GSK1363089) is a multiple receptor tyrosine kinases inhibitor. In this study, a reliable, fast liquid chromatography-tandem mass spectrometric method was described for assaying foretinib in plasma, urine, and rat liver microsome samples. Simple extraction procedure by protein preciptation with acetonitrile was implemented for foretinib and brigatinib (internal standard) analysis. Chromatographic resolution of analytes was achieved on C column with the help of isocratic mobile phase. The binary mobile phase consisted of 60% ammonium formate (10 mM, pH 4.2) and 40% acetonitrile at a flow rate of 0.25 mL/min. Run time was 3 min, and both foretinib and brigatinib were eluted within 0.74 and 1.95 min; they were detected in positive ion mode utilizing multiple reactions monitoring mode. Linearity of the proposed method ranged from 5 to 500 ng/mL (r≥ 0.9993) in the human plasma. Lower limit of quantification and detection were 6.0 and 1.8 ng/mL, respectively. Intraday and interday precision and accuracy were 0.16 to 1.67 % and -2.39 to -0.52 %. In vitro half-life and intrinsic clearance were 24.93 min and 6.56 mL/min/kg, respectively. Literature review showed that no previous studies have been proposed for the analytical quantification of foretinib in human plasma or its metabolic stability. The established method was also applied to estimate the rate of foretinib excretion in rat urine. The developed method can be used for foretinib pharmacokinetic applications.
福瑞替尼（GSK1363089）是一种多受体酪氨酸激酶抑制剂。在本研究中，描述了一种可靠、快速的液相色谱 - 串联质谱法，用于测定血浆、尿液和大鼠肝微粒体样品中的福瑞替尼。采用乙腈沉淀蛋白的简单提取程序进行福瑞替尼和布加替尼（内标）分析。在等度流动相的帮助下，在C柱上实现了分析物的色谱分离。二元流动相由60%甲酸铵（10 mM，pH 4.2）和40%乙腈组成，流速为0.25 mL/min。运行时间为3分钟，福瑞替尼和布加替尼均在0.74和1.95分钟内洗脱；采用多反应监测模式在正离子模式下进行检测。所提出方法在人血浆中的线性范围为5至500 ng/mL（r≥0.9993）。定量下限和检测下限分别为6.0和1.8 ng/mL。日内和日间精密度和准确度分别为0.16%至1.67%和 -2.39%至 -0.52%。体外半衰期和内在清除率分别为24.93分钟和6.56 mL/min/kg。文献综述表明，以前没有关于人血浆中福瑞替尼分析定量或其代谢稳定性的研究报道。所建立的方法还用于估计大鼠尿液中福瑞替尼的排泄率。所开发的方法可用于福瑞替尼的药代动力学应用。
