title: Quantification of sofosbuvir in human serum by liquid chromatography with negative ionization mass spectrometry using the parent peak and its source-induced fragment: Application to a bioequivalence study.
abstract: In the mass spectrometry of sofosbuvir, a new orally administered antihepatitis C drug, a weak peak is detected at the m/z value of the parent ion (m/z 530) as a result of in-source dissociation and current methods to its quantification, is based on monitoring of the parent peak using ultra high-performance liquid chromatography with tandem mass spectrometry. With these methods serum concentration of the drug is quantifiable only up to 4-5 h postdose. However, the fragmentation of the molecule generates a more stable ion at m/z 287 (base peak) with a signal intensity of about tenfold compared to the parent ion. Our study was aimed to improve sensitivity of analysis by acquisition of the m/z value of the daughter ion from which it originated instead of the parent molecule. This novelty allows us to measure serum concentrations of the drug for a longer time postdose and provides more opportunity for pharmacokinetic studies of sofosbuvir. Our method was linear over the concentration range of 2-2560 ng/mL of sofosbuvir in human serum with a limit of quantification of 2 ng/mL compared to 10 ng/mL reported previously. The coefficient variation values of both inter and intraday analysis were less than 13.8%, and the percentage error was less than 6.3.
authors.affiliation: School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Mohammad Taher
authors.initials: MT
authors.lastname: Bahrami
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Bahareh
authors.initials: B
authors.lastname: Mohammadi
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Miraghaei
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Atefeh
authors.initials: A
authors.lastname: Babaei
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Matin
authors.initials: M
authors.lastname: Ghaheri
authors.affiliation: School of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.|Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Gholamreza
authors.initials: G
authors.lastname: Bahrami
mesh_terms: D002853:Chromatography, Liquid; D006801:Humans; D008968:Molecular Conformation; D000069474:Sofosbuvir / Q000097:blood*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000069474:Sofosbuvir
keywords: Bioequivalence study; Mass spectrometry; Sofosbuvir; Source-induced dissociation