Remdesivir (RDV) is the first antiviral drug, approved by the Food and Drug Administration, to treat severe acute respiratory syndrome coronavirus 2. RDV is a relatively new chemical entity, ‘ester prodrug’, with no reported stability profile. Due to the urgency of its use and thus fast production, it is important to develop a stability-indicating method for its assay. Chromatographic separation was carried out on a C18 column (250 × 4.6 mm, 5 µm) with dual detection: diode array at 240 nm and fluorescence at λ_ex/em 245/390 nm. Isocratic elution of acetonitrile and distilled water (acidified with phosphoric acid, pH 4) in the ratio of 55:45 (v/v), respectively, was used. The linearity range using HPLC-diode array detection was 0.1–15 μg/mL, whereas that using fluorimetric detection was 0.05–15 μg/mL. As per the International Conference on Harmonization guidelines, RDV has been degraded by accelerated alkaline, acidic, neutral hydrolysis, oxidative, heat, and photolytic stress conditions. Possible degradation hypothesis of the parent molecule has been suggested and illustrated. The proposed methods have achieved selective determination of the intact drug with no peaks overlapping in all assumptions. Extensive degradation confirms threatened drug stability at thermal and basic hydrolytic stressing. The developed methods were fully validated and proved suitable for quality control routine analysis of RDV in raw material and pharmaceutical dosage forms.

中文翻译：

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酯前药瑞德西韦的加速稳定性研究：最近 FDA 批准的 Covid-19 抗病毒药物使用反相 HPLC 荧光和二极管阵列检测

Remdesivir (RDV) 是美国食品和药物管理局批准的第一种用于治疗严重急性呼吸系统综合症冠状病毒 2 的抗病毒药物。 RDV 是一种相对较新的化学实体，“酯前药”，没有报告稳定性特征。由于其使用的紧迫性和快速生产，开发一种用于其测定的稳定性指示方法非常重要。色谱分离在 C18 柱（250 × 4.6 mm，5 µm）上进行，具有双重检测：二极管阵列在 240 nm 和荧光在λ _ex/em245/390 纳米。分别使用比例为 55:45 (v/v) 的乙腈和蒸馏水（用磷酸酸化，pH 4）等度洗脱。使用 HPLC 二极管阵列检测的线性范围为 0.1–15 μg/mL，而使用荧光检测的线性范围为 0.05–15 μg/mL。根据国际协调会议指南，RDV 已被加速的碱性、酸性、中性水解、氧化、热和光解应力条件降解。已经提出并说明了母体分子的可能降解假设。所提出的方法已经实现了对完整药物的选择性测定，在所有假设中没有峰重叠。广泛的降解证实了在热和碱性水解应力下药物稳定性受到威胁。