Marzouk Hoda M, Rezk Mamdouh R, Gouda Amira S, Abdel-Megied Ahmed M
Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562 Cairo, Egypt.
Zi diligence Biocenter, El-Mokattam, Cairo, Egypt.
Microchem J. 2022 Jan;172:106917. doi: 10.1016/j.microc.2021.106917. Epub 2021 Oct 15.
Modern pharmaceutical analysis is paying a lot of attention to the stability of novel drug formulations as well as establishment of suitable stability-indicating approaches. In the current work, a comprehensive stability-indicating HPLC-DAD method has been developed and validated for determination of favipiravir (FAV) which is a novel and emerging antiviral option in COVID-19 treatment. The stability of FAV was examined under different stress conditions. FAV was found to be susceptible to acid, base hydrolysis and oxidative degradation. Structure elucidation of the forced degradation products was carried out using mass spectrometry (MS) operated in electrospray ionization mode. Effective separation of FAV and its induced degradation products was achieved using isocratic elution mode on Zorbax C column maintained at 30 °C. The mobile phase used was comprised of 25.0 mM phosphate buffer (pH 3.5 ± 0.05) containing 0.1% (w/v) heptane sulphonic acid sodium salt-methanol-acetonitrile (62:28:10, by volume), delivered at flow rate of 1.0 mL/min. The diode array detector signal for FAV was monitored at 321.0 nm over a concentration range of 6.25-250.00 µg/mL. The potential mechanisms for generation of degradation products were postulated through comparison of MS fragmentation pattern of FAV and its degradation products. Moreover, the proposed method was also extended to study the degradation kinetics. Additionally, dissolution profiling of FAV in different media was monitored. Clearly, the suggested approach is accurate, reliable, time-saving, and cost-effective. As a result, it may be utilized for regular quality control and stability assessment of FAV in its tablet dosage form.
现代药物分析非常关注新型药物制剂的稳定性以及建立合适的稳定性指示方法。在当前工作中，已开发并验证了一种用于测定法匹拉韦（FAV）的综合稳定性指示高效液相色谱 - 二极管阵列检测（HPLC - DAD）方法，法匹拉韦是一种用于治疗新冠肺炎的新型抗病毒药物。在不同的应激条件下研究了FAV的稳定性。发现FAV易受酸、碱水解和氧化降解的影响。使用电喷雾电离模式运行的质谱（MS）对强制降解产物进行结构解析。在30℃的Zorbax C柱上采用等度洗脱模式实现了FAV及其诱导降解产物的有效分离。所用流动相由含有0.1%（w/v）庚烷磺酸钠盐 - 甲醇 - 乙腈（体积比为62:28:10）的25.0 mM磷酸盐缓冲液（pH 3.5±0.05）组成，流速为1.0 mL/min。在6.25 - 250.00 μg/mL的浓度范围内，在321.0 nm处监测FAV的二极管阵列检测器信号。通过比较FAV及其降解产物的质谱碎片模式推测了降解产物产生的潜在机制。此外，所提出的方法还扩展用于研究降解动力学。另外，监测了FAV在不同介质中的溶出曲线。显然，所建议的方法准确、可靠、省时且具有成本效益。因此，它可用于FAV片剂剂型的常规质量控制和稳定性评估。
