Aldhafiri Wafaa N, Chhonker Yashpal S, Zhang Yuning, Coutler Don W, McGuire Timothy R, Li Rongshi, Murry Daryl J
Department of Pharmacy Practice and Science, College of Pharmacy, University of Nebraska Medical Center, Omaha, NE 68198, USA.
Department of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Molecules. 2020 Dec 13;25(24):5898. doi: 10.3390/molecules25245898.
MP1 is a novel marinopyrrole analogue with activity in MYCN amplified neuroblastoma cell lines. A rapid, selective, and sensitive liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantitation of MP1 in mouse plasma. Analyte separation was achieved using a Waters Acquity UPLCBEH C18 column (1.7 µm, 100 × 2.1 mm). Mobile phase consisted of 0.1% acetic acid in water (10%) and methanol (90%) at a total flow rate of 0.25 mL/min. The mass spectrometer was operated at unit resolution in the multiple reaction monitoring (MRM) mode, using precursor ion > product ion transitions of 324.10 > 168.30 / for MP1 and 411.95 > 224.15 / for PL-3. The MS/MS response was linear over the concentration range from 0.2-500 ng/mL for MP1, correlation coefficient (r) of 0.988. Precision (% RSD) and accuracy (% bias) were within the acceptable limits as per FDA guidelines. MP1 was stable under storage and laboratory handling conditions. The validated method was successfully applied to assess the solubility, in-vitro metabolism, plasma protein binding, and bio-distribution studies of MP1.
MP1是一种新型的海洋吡咯类似物，对MYCN扩增的神经母细胞瘤细胞系具有活性。开发并验证了一种快速、选择性和灵敏的液相色谱-串联质谱（LC-MS/MS）方法，用于定量小鼠血浆中的MP1。使用沃特世Acquity UPLCBEH C18柱（1.7 µm，100×2.1 mm）实现分析物分离。流动相由0.1%乙酸水溶液（10%）和甲醇（90%）组成，总流速为0.25 mL/min。质谱仪在多反应监测（MRM）模式下以单位分辨率运行，MP1的前体离子>产物离子跃迁为324.10>168.30，PL-3的为411.95>224.15。MP1在0.2 - 500 ng/mL浓度范围内，MS/MS响应呈线性，相关系数（r）为0.988。根据FDA指南，精密度（%RSD）和准确度（%偏差）在可接受范围内。MP1在储存和实验室处理条件下稳定。该验证方法成功应用于评估MP1的溶解度、体外代谢、血浆蛋白结合和生物分布研究。
