Department of Pharmacology and Therapeutics, Fundamental Innovative Oncology Core, National Cancer Center Research Institute, Tokyo, Japan.
Division of Molecular Pharmacology, National Cancer Center Research Institute, Tokyo, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2022 Sep 1;1207:123366. doi: 10.1016/j.jchromb.2022.123366. Epub 2022 Jul 14.
E7130 is a novel microtubule inhibitor and a promising tumor microenvironment ameliorator. Since the amount of the administration in preclinical study is very small due to the high potency of E7130, this study aimed to establish a sensitive analytical method to measure E7130 concentration in mouse plasma samples obtained via microsampling. A sensitive and validated method was developed based on ultra-performance liquid chromatography coupled with high-resolution mass spectrometry (UHPLC-HRMS). Chromatographic separation was achieved using a Waters ACQUITY UPLC BEH C18 1.7 µm (2.1 × 50 mm) column. Mobile phase A comprised 0.1% formic acid and 10 mM ammonium formate in water, and mobile phase B was methanol. A gradient elution was applied at a flow rate of 0.5 mL/min. The calibration curve drawn was linear in the 0.2-100 ng/mL E7130 concentration range for mouse plasma microsamples (10 µL). Analytical results demonstrated good precision (<6.7%) and accuracy (88.5%-100.0%) in E7130 quantitation, indicating that UHPLC-HRMS is a useful method for pharmacokinetic analysis and a valuable approach for the quantitation of hardly fragmented compounds.
E7130 是一种新型的微管抑制剂，也是一种很有前途的肿瘤微环境改善剂。由于 E7130 的高功效，在临床前研究中，由于给药量非常少，因此本研究旨在建立一种灵敏的分析方法，以测量从小鼠血浆样品中获得的 E7130 浓度，这些样品是通过微采样获得的。本研究基于超高效液相色谱-高分辨率质谱（UHPLC-HRMS）建立了一种灵敏且经过验证的方法。使用 Waters ACQUITY UPLC BEH C18 1.7 µm（2.1 × 50 mm）柱实现色谱分离。流动相 A 由水中 0.1%甲酸和 10 mM 甲酸铵组成，流动相 B 为甲醇。以 0.5 mL/min 的流速进行梯度洗脱。对于小鼠血浆微样品（10 µL），绘制的校准曲线在 0.2-100 ng/mL E7130 浓度范围内呈线性。E7130 定量分析的结果表明，该方法具有良好的精密度（<6.7%）和准确度（88.5%-100.0%），这表明 UHPLC-HRMS 是一种用于药代动力学分析的有用方法，也是对难分解化合物进行定量的有价值方法。
