Development and validation of a sensitive, fast and simple LC-MS/MS method for the quantitation of favipiravir in human serum
Küçük Resim Yok
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Favipiravir is a broad-spectrum inhibitor of viral RNA polymerase. It is currently used as a possible treatment for coronavirus disease 2019 (COVID-19). Pre-clinical or clinical trials of favipiravir require robust, sensitive, and accurate bioanalytical methods for quantitation of favipiravir levels. Recently, several studies have been reported about developing a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring favipiravir levels. However, these methods were validated predominantly for plasma samples, electrospray ionization was operated only in negative or positive mode, and clinical application of these methods has not been applied for patients with COVID-19. This study aimed was to develop a validated LC-MS/MS method for the measurement of favipiravir levels in positive and negative electrospray ionization mode and to perform a pilot study in patients with COVID-19 receiving favipiravir to demonstrate the applicability of this method in biological samples. Simple protein precipitation was used for the extraction of favipiravir from the desired matrix. Favipiravir levels were quantitated using MS / MS with an electrospray ionization source in positive and negative multiple reaction monitoring (MRM) mode. The chromatographic detection was performed on a reverse-phase Phenomenex C18 column (50 mm x 4.6 mm, 5 mu m, 100 angstrom) with gradient elution using 0.1% formic acid in water and 0.1% formic acid in methanol as mobile phase. The method was linear over the concentration ranges of 0.048-50 mu g/mL (in negative ionization mode) and 0.062-50 mu g/mL (in positive ionization mode) with a correlation coefficient (r2) better than 0.998. The total run time was 3.5 min. The intra-assay and inter-assay % CV values were less than 7.2% and 8.0%, respectively. A simple, rapid and robust LC-MS / MS method was developed for the measurement of favipiravir and validation studies were performed. The validated method was successfully applied for drug level measurement in COVID-19 patients receiving favipiravir.
Açıklama
Anahtar Kelimeler
Favipiravir, Covid-19, Tandem Mass Spectrometry, Validation
Kaynak
Journal Of Chromatography B-Analytical Technologies In The Biomedical And Life Sciences
WoS Q Değeri
Q2
Scopus Q Değeri
Q2
Cilt
1176
