Development and validation of an LC-MS/MS method for quantification of favipiravir in human plasma
Development and validation of an LC-MS/MS method for quantification of favipiravir in human plasma
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DOI：
10.1016/j.jpba.2023.115436
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发表时间：
2023-05-04
影响因子：
3.4
通讯作者：
Else, Laura
中科院分区：
文献类型：
--
作者：
Challenger, Elizabeth;Penchala, Sujan Dilly;Else, Laura
Favipiravir （FVP）是一种广谱抗病毒药物，可选择性抑制病毒RNA依赖性RNA聚合酶，首次用于治疗流感感染。它已被证明对许多RNA病毒家族有效，包括沙粒病毒、黄病毒和肠病毒。最近，人们研究了FVP作为严重急性呼吸综合征冠状病毒2感染的潜在治疗方法。已经开发并验证了一种用于定量人血浆中FVP的液相色谱串联质谱方法，用于研究favipiravir治疗冠状病毒病-2019的临床试验。以13C， 15N- Favipiravir为内标，乙腈沉淀蛋白提取样品。采用由0.2%甲酸水溶液和0.2%甲酸甲醇组成的梯度流动相程序，在Synergi Polar-RP 150 x 2.1 mm 4 μ m色谱柱上进行洗脱。在500-50,000 ng/mL范围内验证；结果表明，该方法精密度高，回收率高。稳定性实验证实并扩展了FVP的已知稳定性，包括热处理和在- 80℃下持续10个月的稳定性。
Favipiravir (FVP) is a broad-spectrum antiviral that selectively inhibits viral RNA-dependent RNA polymerase, first trialled for the treatment of influenza infection. It has been shown to be effective against a number of RNA virus families including arenaviruses, flaviviruses and enteroviruses. Most recently, FVP has been investigated as a potential therapeutic for severe acute respiratory syndrome coronavirus 2 infection. A liquid chromatography tandem mass spectrometry method for the quantification of FVP in human plasma has been developed and validated for use in clinical trials investigating favipiravir as treatment for coronavirus disease-2019. Samples were extracted by protein precipitation using acetonitrile, using 13C, 15N- Favipiravir as internal standard. Elution was performed on a Synergi Polar-RP 150 x 2.1 mm 4 mu m column using a gradient mobile phase programme consisting of 0.2% formic acid in water and 0.2% formic acid in methanol. The assay was validated over the range 500-50,000 ng/mL; this method was found to be precise and accurate and recovery of FVP from the matrix was high. Stability experiments confirmed and expanded on the known stability of FVP, including under heat treatment and for a period of 10 months at - 80 degrees C.