Analytical Chemistry Department, Faculty of Pharmacy, Zagazig University, Zagazig 44511, Egypt.
Institute of Medicinal and Pharmaceutical Chemistry, Technische Universitaet Braunschweig, 38106 Braunschweig, Germany.
Molecules. 2022 Apr 4;27(7):2330. doi: 10.3390/molecules27072330.
Following the spread of the COVID-19 pandemic crisis, a race was initiated to find a successful regimen for postinfections. Among those trials, a recent study declared the efficacy of an antiviral combination of favipiravir (FAV) and molnupiravir (MLP). The combined regimen helped in a successful 60% eradication of the SARS-CoV-2 virus from the lungs of studied hamster models. Moreover, it prevented viral transmission to cohosted sentinels. Because both medications are orally bioavailable, the coformulation of FAV and MLP can be predicted. The developed study is aimed at developing new green and simple methods for the simultaneous determination of FAV and MLP and then at their application in the study of their dissolution behavior if coformulated together. A green micellar HPLC method was validated using an RP-C18 core-shell column (5 μm, 150 × 4.6 mm) and an isocratic mixed micellar mobile phase composed of 0.1 M SDS, 0.01 M Brij-35, and 0.02 M monobasic potassium phosphate mixture and adjusted to pH 3.1 at 1.0 mL min flow rate. The analytes were detected at 230 nm. The run time was less than five minutes under the optimized chromatographic conditions. Four other multivariate chemometric model methods were developed and validated, namely, classical least square (CLS), principal component regression (PCR), partial least squares (PLS-1), and genetic algorithm-partial least squares (GA-PLS-1). The developed models succeeded in resolving the great similarity and overlapping in the FAV and MLP UV spectra unlike the traditional univariate methods. All methods were organic solvent-free, did not require extraction or derivatization steps, and were applied for the construction of the simultaneous dissolution profile for FAV tablets and MLP capsules. The methods revealed that the amount of the simultaneously released cited drugs increases up until reaching a plateau after 15 and 20 min for FAV and MLP, respectively. The greenness was assessed on GAPI and found to be in harmony with green analytical chemistry concepts.
随着 COVID-19 大流行危机的蔓延，人们开始竞相寻找有效的抗感染治疗方案。在这些试验中，最近的一项研究宣布了法匹拉韦（FAV）和莫努匹韦（MLP）联合抗病毒的疗效。联合治疗方案成功地将受感染仓鼠模型肺部的 SARS-CoV-2 病毒清除了 60%。此外，它还阻止了病毒向共同饲养的哨兵的传播。由于这两种药物均可口服生物利用，因此可以预测 FAV 和 MLP 的联合制剂。本研究旨在开发新的绿色简单方法，用于同时测定 FAV 和 MLP，然后在联合应用时研究其溶解行为。采用反相 C18 核壳柱（5 μm，150×4.6 mm）和等度混合胶束流动相，由 0.1 M SDS、0.01 M Brij-35 和 0.02 M 单磷酸二氢钾混合物组成，并用 1.0 mL min 的流速调节 pH 值至 3.1，建立了绿色胶束高效液相色谱法。在 230nm 处检测到分析物。在优化的色谱条件下，运行时间不到五分钟。还开发并验证了其他四种多元化学计量模型方法，即经典最小二乘法（CLS）、主成分回归（PCR）、偏最小二乘法（PLS-1）和遗传算法偏最小二乘法（GA-PLS-1）。与传统的单变量方法不同，所开发的模型成功地解决了 FAV 和 MLP 的紫外光谱之间的巨大相似性和重叠问题。所有方法均为无有机溶剂，无需提取或衍生化步骤，并应用于 FAV 片剂和 MLP 胶囊的同时溶出度曲线的构建。这些方法表明，同时释放的参比药物的数量在 FAV 和 MLP 分别达到 15 和 20 分钟的平台后增加。绿色度通过 GAPI 进行评估，发现与绿色分析化学概念一致。
