Hacettepe University, Faculty of Pharmacy, Department of Analytical Chemistry, 06100 Sıhhiye, Ankara, Turkey.
Hacettepe University, Faculty of Pharmacy, Department of Pharmaceutical Technology, 06100 Sıhhiye, Ankara, Turkey.
J Pharm Biomed Anal. 2022 May 30;214:114693. doi: 10.1016/j.jpba.2022.114693. Epub 2022 Feb 26.
Antiviral drugs have gained much more attention in recent years due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and many drug candidates are currently under investigation in order to end pandemic. Molnupiravir, a prodrug of the synthetic nucleoside derivative N4-hydroxycytidine, is one of the promising candidates for SARS-CoV-2 treatment. In this study, a RP-HPLC method was developed for the determination of Molnupiravir and applied for in vitro permeability studies of self-emulsifying drug delivery system (SEDDS) formulations using Caco-2 cell line. Discovery® HS C18 Column (75 ×4.6 mm, 3 µm) was used at 30 °C. Isocratic elution was performed with ACN:water (20:80 v/v) mixture. The flow rate was 0.5 mL/min and UV detection was at 240 nm. Molnupiravir eluted within 5 min. Molnupiravir was exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions. Peak homogeneity data of Molnupiravir in the stressed samples peak obtained using photodiode array detector, in the stressed sample chromatograms, demonstrated the specificity of the method for their estimation in presence of degradants. The developed method was validated according to the International Council for Harmonisation (ICH) guidelines and found to be linear within the range 0.1-60.0 μg/mL. The method was simple, rapid, selective, sensitive, accurate, precise, robust and rugged. Thus, it was applied successfully for permeability quantitation of Molnupiravir in nanoformulations. The apparent permeability of Molnupiravir in SEDDS formulations, which have droplet size under 350 nm, was calculated as 3.20 ± 0.44 × 10 cm/s.
由于严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）感染，抗病毒药物近年来受到了更多关注，目前有许多候选药物正在研究中，以期结束大流行。Molnupiravir 是合成核苷衍生物 N4-羟基胞苷的前药，是治疗 SARS-CoV-2 的有前途的候选药物之一。在这项研究中，开发了一种用于测定 Molnupiravir 的反相高效液相色谱法，并应用于使用 Caco-2 细胞系的自乳化药物递送系统（SEDDS）制剂的体外渗透研究。Discovery®HS C18 柱（75×4.6mm，3μm）在 30°C 下使用。采用 ACN:水（20:80 v/v）混合物进行等度洗脱。流速为 0.5mL/min，UV 检测波长为 240nm。Molnupiravir 在 5 分钟内洗脱。Molnupiravir 暴露于热、光解、水解和氧化应激条件下。使用光电二极管阵列检测器获得的应激样品峰中的 Molnupiravir 峰均一性数据，在应激样品色谱图中，证明了该方法对其在降解产物存在下的估计的专属性。所开发的方法根据国际协调会议（ICH）指南进行了验证，发现其在 0.1-60.0μg/mL 范围内呈线性。该方法简单、快速、选择性好、灵敏、准确、精密、耐用且稳定。因此，它成功地应用于纳米制剂中 Molnupiravir 渗透性的定量。SEDDS 制剂中 Molnupiravir 的表观渗透性，其液滴尺寸小于 350nm，计算为 3.20±0.44×10 cm/s。
