Alrubia Sarah, AlShehri Wafa A, Radwan Awwad A, Alzoman Nourah Z, Darwish Ibrahim A
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh, 11451, Saudi Arabia.
BMC Chem. 2025 Jan 29;19(1):27. doi: 10.1186/s13065-024-01353-6.
For paediatric patients suffering from neurofibromatosis, Selumetinib (SEL) is the only approved drug. Here an original ecofriendly and high pace method is introduced using 96- microwell spectrophotometric assay (MW-SPA) to measure SEL content in bulk and commercial pharmaceutical formulation (Koselugo capsules). This assay was relied on in-microwell formation of a coloured charge transfer complex (CTC) upon interaction of SEL with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The complex was fully characterized by spectrophotometric and computational studies. The CTC exhibited an absorbance maximum (λ) at 440 nm. The ease of reaction occurrence, complex stability and its high absorptivity were proved by measuring its association constant (0.63 × 10 L/ mol), standard free energy change (-10.31 KJ/mol), molar absorptivity (ε) (3.78 × 10 L/mol/cm), and the SEL: DDQ stoichiometric ratio (1:1). Establishments of the optimum values of the applied conditions in 96-well assay plate were refined regarding DDQ concentration, reaction time, temperature, and solvents. Validation of the assay was according to the ICH guidelines. The assay was linear in SEL' concentrations ranged from 10 to 200 µg/well, with limits of detection and quantitation of 4.1 and 12.5 µg/well, respectively. Then, the assay was efficaciously adapted to accurately and precisely determine SEL content in bulk form and Koselugo capsules. The assay environmental safety was documented by three different comprehensive metric tools. Additionally, assessment of the assay's rate demonstrated its high throughput, enabling the processing of large number of samples in pharmaceutical quality control laboratories. The successful development of this assay provides a valuable fast and green analytical tool for ensuring the quality control of SEL's bulk form and capsules.
对于患有神经纤维瘤病的儿科患者，司美替尼（SEL）是唯一获批的药物。本文介绍了一种原始的环保且高效的方法，即使用96孔分光光度法（MW-SPA）来测定原料药和市售药物制剂（科斯美妥胶囊）中的司美替尼含量。该测定方法基于司美替尼与2,3-二氯-5,6-二氰基-1,4-苯醌（DDQ）相互作用时在微孔中形成有色电荷转移络合物（CTC）。通过分光光度法和计算研究对该络合物进行了全面表征。该CTC在440 nm处呈现最大吸光度（λ）。通过测量其缔合常数（0.63×10 L/mol）、标准自由能变化（-10.31 KJ/mol）、摩尔吸光系数（ε）（3.78×10 L/mol/cm）以及司美替尼与DDQ的化学计量比（1:1），证明了反应易于发生、络合物稳定性及其高吸光率。针对DDQ浓度、反应时间、温度和溶剂，对96孔测定板中应用条件的最佳值进行了优化。该测定方法按照国际人用药品注册技术协调会（ICH）指南进行验证。该测定方法在司美替尼浓度为10至200 µg/孔范围内呈线性，检测限和定量限分别为4.1和12.5 µg/孔。然后，该测定方法有效地适用于准确且精确地测定原料药和科斯美妥胶囊中的司美替尼含量。通过三种不同的综合度量工具证明了该测定方法的环境安全性。此外，对该测定方法的速率评估表明其具有高通量，能够在药物质量控制实验室中处理大量样品。该测定方法的成功开发为确保司美替尼原料药和胶囊的质量控制提供了一种有价值的快速且绿色的分析工具。
