Institut des Biomolécules Max Mousseron (IBMM), UMR 5247-CNRS-UM-ENSCM, Montpellier, France.
Department of Analytical Chemistry, Faculty of Pharmacy, Misr University of Science and Technology (MUST)., 6th of October City, Egypt.
Electrophoresis. 2019 Nov;40(21):2810-2819. doi: 10.1002/elps.201900188. Epub 2019 Sep 2.
A simple, sensitive, specific, and cost-effective analytical methodology was developed for the analysis of human plasma samples spiked with imatinib by CZE with on-line UV detection in the context of Therapeutic Drug Monitoring. Several analytical conditions such as the ionic strength (I) and the pH of the BGE composed of citric acid and ε-amino caproic acid were studied in regards of the presence of sodium chloride (NaCl) in plasma samples (1% m/v). Computer simulations (Simul software) were used to confirm the experimental results and to understand imatinib electrophoretic behavior in the presence of NaCl. Furthermore, the advantages of adding ACN to the sample containing NaCl to combine efficient protein precipitation and on-line CZE stacking of imatinib were demonstrated. LOD and LOQ values of 48 and 191 ng/mL were obtained from plasma sample supernatant after protein precipitation with ACN, which is much lower than mean imatinib plasma level observed for patients treated by imatinib mesylate (about 1000 ng/mL). Good linearity was obtained in the concentration range 191-5000 ng/mL (R > 0.997). RSD of less than 1.68% and 2.60% (n = 6) for migration times and corrected peak areas, respectively, were observed at the LOQ.
建立了一种简单、灵敏、特异、经济的分析方法，用于在治疗药物监测中分析人血浆样品中添加伊马替尼的情况。在含有氯化钠（NaCl）的血浆样品（1%m/v）中，研究了由柠檬酸和ε-氨基己酸组成的 BGE 的离子强度（I）和 pH 等多种分析条件。计算机模拟（Simul 软件）用于确认实验结果并理解存在 NaCl 时伊马替尼的电泳行为。此外，还证明了在含有 NaCl 的样品中添加 ACN 以结合有效的蛋白质沉淀和在线 CZE 堆积伊马替尼的优势。通过 ACN 沉淀蛋白质后，从血浆样品上清液中获得 48 和 191ng/mL 的 LOD 和 LOQ 值，远低于接受甲磺酸伊马替尼治疗的患者的平均伊马替尼血浆水平（约 1000ng/mL）。在 191-5000ng/mL 的浓度范围内获得了良好的线性关系（R>0.997）。在 LOQ 时，分别观察到迁移时间和校正峰面积的 RSD 小于 1.68%和 2.60%（n=6）。
