Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nahda University (NUB), Beni-Suef, 62511, Egypt.
Sci Rep. 2024 Mar 22;14(1):6869. doi: 10.1038/s41598-024-53456-8.
Hydroxychloroquine (HCQ) is prescribed to treat malaria and certain autoimmune diseases. Recent studies questioned its efficiency in relieving COVID-19 symptoms and improving clinical outcomes. This work presents a quality-by-design approach to develop, optimize, and validate a potentiometric sensor for the selective analysis of HCQ in the presence of its toxic impurities (key starting materials), namely 4,7-Dichloroquinoline (DCQ) and hydroxynovaldiamine (HND). The study employed a custom experimental design of 16 sensors with different ion exchangers, plasticizers, and ionophores. We observed the Nernstian slopes, correlation coefficients, quantification limit, response time, and selectivity coefficient for DCQ and HND. The computer software constructed a prediction model for each response. The predicted responses strongly correlate to the experimental ones, indicating model fitness. The optimized sensor achieved 93.8% desirability. It proved a slope of 30.57 mV/decade, a correlation coefficient of 0.9931, a quantification limit of 1.07 × 10 M, a detection limit of 2.18 × 10 M, and a fast response of 6.5 s within the pH range of 2.5-8.5. The sensor was successfully used to determine HCQ purity in its raw material. The sensor represents a potential tool for rapid, sensitive, and selective monitoring of HCQ purity during industrial production from its starting materials.
羟氯喹 (HCQ) 被用于治疗疟疾和某些自身免疫性疾病。最近的研究对其缓解 COVID-19 症状和改善临床结果的效果提出了质疑。本工作提出了一种质量源于设计的方法，用于开发、优化和验证一种用于选择性分析 HCQ 的离子选择性电极传感器，同时存在其有毒杂质（关键起始材料），即 4,7-二氯喹啉 (DCQ) 和羟乙二肟 (HND)。该研究采用了 16 个具有不同离子交换剂、增塑剂和离子载体的传感器的定制实验设计。我们观察了 DCQ 和 HND 的 Nernst 斜率、相关系数、定量限、响应时间和选择性系数。计算机软件为每个响应构建了一个预测模型。预测响应与实验响应强烈相关，表明模型拟合度良好。优化后的传感器达到了 93.8%的理想度。它证明了 30.57 mV/decade 的斜率、0.9931 的相关系数、1.07 × 10 M 的定量限、2.18 × 10 M 的检测限，以及在 2.5-8.5 pH 范围内的 6.5 s 的快速响应。该传感器成功地用于测定其原材料中 HCQ 的纯度。该传感器代表了一种用于从起始材料快速、灵敏和选择性监测 HCQ 纯度的潜在工具，可用于工业生产过程中。
