Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut branch, Assiut, Egypt.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut branch, Assiut, Egypt.
Arch Pharm (Weinheim). 2023 Jun;356(6):e2300005. doi: 10.1002/ardp.202300005. Epub 2023 Apr 3.
The endemicity of the pandemic coronavirus disease 2019 (COVID-19) infection proved to be transitional only. Spikes are forming again in 2023, and high expectations are returning for reinfections and viral mutations. Molnupiravir (MOL) has been approved as an oral antiviral drug for the treatment of the COVID-19 causative virion. Therefore, the development of an ultrasensitive, instantaneous, and cost-effective method for the quantification of MOL in real plasma samples and formulated dosage form are mandatory. The proposed approach is based on the synthesis of a MOL metal-chelation product. MOL as a ligand was chelated with 1.0 mM zinc(II) in an acetate buffer (pH 5.3). After illumination at 340 nm, the intensity of the MOL fluorescence measured at 386 nm was increased by about 10-fold. The linearity range was found to be from 60.0 to 800.0 ng mL with limit of quantitation (LOQ) of 28.6 ng mL . Two methods were utilized for measuring the greenness of the proposed method (Green Analytical Procedure Index [GAPI] and analytical greenness metric [AGREE] methods), with results equal to 0.8. The binding stoichiometry of MOL with the zinc(II) ion was found to be 2:1. All the experimental parameters were optimized and validated using International Conference on Harmonization (ICH) and United States Food and Drug Administration (US-FDA) recommendations. Furthermore, the fluorescent probes were successfully utilized in real human plasma with high percentages of recovery (95.6%-97.1%) without any matrix interferences. The mechanism of fluorescent complex formation was confirmed using H NMR in the presence and absence of Zn(II). The method was further utilized for testing content uniformity of MOL in its marketed capsule dosage forms.
2019 年冠状病毒病（COVID-19）大流行的地方性证明是过渡性的。2023 年再次出现高峰，人们对再次感染和病毒突变的期望再次升高。莫努匹韦（MOL）已被批准为治疗 COVID-19 致病病毒的口服抗病毒药物。因此，开发一种超灵敏、瞬时和具有成本效益的方法来定量测定真实血浆样品和配方剂型中的 MOL 是强制性的。所提出的方法基于 MOL 金属螯合物产物的合成。MOL 作为配体与醋酸盐缓冲液（pH 5.3）中的 1.0 mM 锌（II）螯合。在 340nm 光照后，测量到的 386nm 处的 MOL 荧光强度增加了约 10 倍。发现线性范围为 60.0 至 800.0ngmL，检出限（LOQ）为 28.6ngmL。两种方法（绿色分析程序指数[GAPI]和分析绿色度指标[AGREE]方法）用于测量所提出方法的绿色度，结果等于 0.8。发现 MOL 与锌（II）离子的结合化学计量比为 2:1。根据国际协调会议（ICH）和美国食品和药物管理局（US-FDA）的建议，优化和验证了所有实验参数。此外，荧光探针已成功用于真实的人血浆中，回收率高达 95.6%-97.1%，没有任何基质干扰。在存在和不存在 Zn(II)的情况下使用 1 H NMR 证实了荧光配合物形成的机制。该方法进一步用于测试其市售胶囊剂型中 MOL 的含量均匀度。
