Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia.
Clin Chim Acta. 2018 May;480:180-185. doi: 10.1016/j.cca.2018.02.016. Epub 2018 Feb 16.
Brigatinib (BGB) belongs to a class of drugs called ALK inhibitor. On April 28, 2017, BGB has been approved by U.S. FDA for use in metastatic ALK-positive NSCLC. A fast, specific, sensitive and validated LC-MS/MS method was developed for the quantification of BGB in human plasma matrix. This method was applied successfully to study metabolic stability of BGB. Reversed phase (C18 column) and isocratic binary mobile phase (55% 0.1% formic acid: 45% ACN) were used for chromatographic separation of BGB and ponatinib (IS). The flow rate, total run time and injection volume were fixed at 0.2 mL/min, 4 min, 5 μL respectively. ESI source was utilized for ions formation, while multiple reaction monitoring (MRM) mode was used for ion analysis. In human plasma matrix, the Linearity range of the calibration curve was 5-500 ng/mL (r ≥ 0.9982). LOQ and LOD were found to be 1.89 and 5.72 ng/mL. The precision and accuracy for the intra-day and inter-day were 0.45 to 1.85% and 97.37 to 104.85%. In vitro half-life (t) and intrinsic clearance (CL) were equal to 12.0 min and 13.1 ± 0.15 mL/min/kg respectively. The quantification of BGB in human plasma or its metabolic stability has not been studied as seen in literature review.
布加替尼（BGB）属于一类称为 ALK 抑制剂的药物。2017 年 4 月 28 日，BGB 已获得美国 FDA 批准用于转移性 ALK 阳性 NSCLC。建立了一种快速、特异、灵敏和验证的 LC-MS/MS 方法，用于人血浆基质中 BGB 的定量。该方法成功应用于 BGB 代谢稳定性的研究。反相（C18 柱）和等度二元流动相（55%0.1%甲酸：45%ACN）用于 BGB 和 ponatinib（IS）的色谱分离。流速、总运行时间和进样体积分别固定在 0.2mL/min、4min 和 5μL。ESI 源用于离子形成，而多反应监测（MRM）模式用于离子分析。在人血浆基质中，校准曲线的线性范围为 5-500ng/mL（r≥0.9982）。LOQ 和 LOD 分别为 1.89 和 5.72ng/mL。日内和日间精密度和准确度分别为 0.45-1.85%和 97.37-104.85%。体外半衰期（t）和内在清除率（CL）分别为 12.0 分钟和 13.1±0.15mL/min/kg。文献综述未见 BGB 在人血浆中的定量或代谢稳定性研究。
