Park Changmin, Ha Joong Gyu, Choi Seungmok, Kim Eunyoung, Noh Keumhan, Shin Beom Soo, Kang Wonku
College of Pharmacy, Chung-Ang University, Seoul 06974, South Korea.
Department of Obstetrics and Gynecology, Eulji University Hospital, Eulji University School of Medicine, Daejeon 35233, South Korea.
J Pharm Biomed Anal. 2018 Feb 20;150:39-42. doi: 10.1016/j.jpba.2017.12.002. Epub 2017 Dec 5.
Mesupron, the first-in-class inhibitor of urokinase-type plasminogen activator (uPA) is known to regulate cell proliferation and migration, and is under investigation for the treatment of metastatic breast cancer. In this study, a quantification method was developed for the determination of mesupron in rat plasma using liquid chromatography with a tandem mass spectrometry (LC-MS/MS). After protein precipitation with acetonitrile including itraconazole (internal standard, IS), the analytes were chromatographed on a reversed phased column with a mobile phase of acetonitrile and water (7:3, v/v, including 0.1% formic acid). The ion transitions of the precursor to the product ion were principally protonated ion [M+H] at m/z 630.4→398.3 for mesupron and 705.2→392.1 for the IS. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods This method was successfully applied to a pharmacokinetic study of mesupron after intravenous administration in rats.
美舒普隆是尿激酶型纤溶酶原激活剂（uPA）的同类首创抑制剂，已知其可调节细胞增殖和迁移，目前正在进行转移性乳腺癌治疗的研究。在本研究中，开发了一种使用液相色谱-串联质谱法（LC-MS/MS）测定大鼠血浆中美舒普隆的定量方法。在用含伊曲康唑（内标，IS）的乙腈进行蛋白沉淀后，分析物在反相柱上进行色谱分离，流动相为乙腈和水（7:3，v/v，含0.1%甲酸）。美舒普隆的前体离子到产物离子的离子跃迁主要为质子化离子[M+H]，m/z为630.4→398.3，内标的离子跃迁为705.2→392.1。该分析方法的准确度和精密度符合FDA生物分析方法验证法规要求。该方法已成功应用于大鼠静脉注射美舒普隆后的药代动力学研究。
