Istanbul Technical University, Faculty of Sciences and Letters, Department of Chemistry, Maslak, Istanbul, Türkiye.
Kocaeli University, Kocaeli Vocational School, Department of Chemistry and Chemical Processing Technologies, Kocaeli, 41140, Türkiye.
J Chromatogr B Analyt Technol Biomed Life Sci. 2024 Feb 15;1234:124019. doi: 10.1016/j.jchromb.2024.124019. Epub 2024 Jan 26.
Atypical antidepressant mirtazapine (MIR) is mostly prescribed for the management of major depressive disorder. The identification of MIR in pharmaceutical dosage forms was made possible by developing a novel, quick, sensitive high-performance liquid chromatography (HPLC) approach that was verified in accordance with ICH recommendations. In the first part of this study, HPLC investigations were optimized with regard to variables including pH, working column, mobile phase, temperature, and flow rate. The limit of detection (LOD) was 0.013 ppm, the limit of quantification (LOQ) was 0.044 ppm, and the linear range was computed as 0.5-15 ppm (R = 0.9998). The recovery investigation assessed the method's accuracy, which was shown to range between 98.82 and 100.97 %. In the second part, by using UV-vis spectroscopy, HPLC, thermal denaturation, and viscosity measurements, the mechanism of binding interaction of MIR with double-stranded fish sperm deoxyribonucleic acid (dsDNA) has been thoroughly studied. The DNA binding constants (K) were determined using UV-Vis absorption and HPLC methods. To investigate the interactions of MIR with dsDNA, molecular docking calculations and additionally, molecular dynamics simulations were performed. Results showed that MIR is located in the minor groove of dsDNA, and in addition to hydrogen bonding, electrostatic interaction is also formed between the aromatic ring of MIR and phosphate oxygen of dsDNA. Finally, a binding characterization study using MIR tablets was also conducted in order to assess the interaction mechanism of the DNA with the drug using the validated analytical procedure developed for the MIR molecule.
米氮平（MIR）是一种非典型抗抑郁药，主要用于治疗重度抑郁症。本研究建立了一种新型、快速、灵敏的高效液相色谱（HPLC）法，可用于药物制剂中米氮平的鉴别，并按照 ICH 建议进行了验证。在本研究的第一部分，通过对 pH 值、工作柱、流动相、温度和流速等变量进行优化，对 HPLC 进行了研究。检测限（LOD）为 0.013ppm，定量限（LOQ）为 0.044ppm，线性范围为 0.5-15ppm（R=0.9998）。回收率研究评估了该方法的准确性，结果表明其在 98.82%至 100.97%之间。在第二部分，通过使用紫外可见光谱法、HPLC、热变性和粘度测量法，深入研究了 MIR 与双链鱼精脱氧核糖核酸（dsDNA）的结合相互作用机制。使用紫外可见吸收法和 HPLC 法测定 DNA 结合常数（K）。为了研究 MIR 与 dsDNA 的相互作用，进行了分子对接计算和分子动力学模拟。结果表明，MIR 位于 dsDNA 的小沟中，除氢键外，MIR 的芳环与 dsDNA 的磷酸氧之间还形成了静电相互作用。最后，还使用 MIR 片剂进行了结合特征研究，以使用为 MIR 分子开发的经过验证的分析程序评估药物与 DNA 的相互作用机制。
