Pethani Trupesh M, Sangani Monika, Santoki Param S
Department of Pharmaceutical Sciences, Saurashtra University, University Road, Rajkot 360 005, Gujarat, India.
J Chromatogr Sci. 2025 Mar 27;63(4). doi: 10.1093/chromsci/bmaf015.
Coronavirus disease 2019 (COVID-19) is a disease caused by a virus named SARS-CoV-2. It is very contagious and has quickly spread around the world. COVID-19 most often causes respiratory symptoms that can feel much like a cold, a flu, or pneumonia. Molnupiravir (MLP) and Favipiravir (FAV) are two recently approved drugs for the ongoing COVID-19 pandemic drug combination help to reduce antiviral load with less side effect. MLP and Favipiravir standards subjected to degradation under different stress condition like acidic, basic, oxidative, thermal, and photostability. The current study endeavors to identify and characterize the degradation products of MLP and Favipiravir using Liquid Chromatography-Mass Spectrometry (LC-MS). Method developed and validated as per International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use Guideline (ICH) Q2(R1). The high performance liquid chromatography separation was achieved using Phenomenex Gemini 5 μ C18 (250 mm × 4.6 mm, 5 μm) column using mobile phase A and mobile phase B (15: 85% V/V) and the composition of mobile phase A: 10 mM ammonium acetate and mobile phase B: Acetonitrile (ACN) and methanol 70:30% V/V. Injection volume of 10 μL with 1.0 mL/min flow rate. The detection wavelength was 275 nm and the study was performed at 40°C column temperature. Excellent linear relationship between peak area of MLP and Favipiravir concentration in the range of 5-500 μg/mL for both drugs has been observed R2 = 0.9995 and R2 = 0.9996, respectively. Precision, accuracy, and robustness were found to be < 2% in terms of Relative Standard Deviation (RSD) and all other parameter were found within the specified criteria as per ICH guidelines. Proposed method has been successfully applied for quantification of MLP and Favipiravir in the presence of its impurities.
2019冠状病毒病（COVID-19）是一种由名为严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的病毒引起的疾病。它具有很强的传染性，并已迅速在全球传播。COVID-19最常引起的呼吸道症状与感冒、流感或肺炎非常相似。莫努匹拉韦（MLP）和法匹拉韦（FAV）是最近批准用于当前COVID-19大流行的两种药物，药物组合有助于降低抗病毒负荷且副作用较小。MLP和法匹拉韦标准品在不同的应激条件下会发生降解，如酸性、碱性、氧化、热和光稳定性条件。本研究致力于使用液相色谱-质谱联用仪（LC-MS）鉴定和表征MLP和法匹拉韦的降解产物。所开发的方法根据人用药品注册技术要求国际协调理事会（ICH）Q2（R1）指南进行了验证。使用菲罗门Gemini 5 μ C18（250 mm×4.6 mm，5 μm）色谱柱进行高效液相色谱分离，流动相A和流动相B（15:85% V/V），流动相A的组成：10 mM醋酸铵，流动相B：乙腈（ACN）和甲醇70:30% V/V。进样体积为10 μL，流速为1.0 mL/min。检测波长为275 nm，研究在柱温40°C下进行。两种药物在5-500 μg/mL范围内，MLP和法匹拉韦浓度与峰面积之间均呈现出良好的线性关系，R2分别为0.9995和0.9996。就相对标准偏差（RSD）而言，精密度、准确度和稳健性均<2%，并且所有其他参数均符合ICH指南规定的标准。所提出的方法已成功应用于在有杂质存在的情况下对MLP和法匹拉韦进行定量分析。
