title: Novel and sensitive UPLC-MS/MS method for quantification of sofosbuvir in human plasma: application to a bioequivalence study.
abstract: A novel and sensitive LC-MS/MS method was developed and validated for determination of sofosbuvir (SF) using eplerenone as an internal standard. The Xevo TQD LC-MS/MS was operated under the multiple-reaction monitoring mode using electrospray ionization. Extraction with tert-butyl methyl ether was used in sample preparation. The prepared samples were chromatographed on Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 μm) column by pumping 0.1% formic acid and acetonitrile in an isocratic mode at a flow rate of 0.35 mL/min. Method validation was performed as per the US Food and Drug Administration guidelines and the standard curves were found to be linear in the range of 0.25-3500 ng/mL for SF. The intra- and inter-day precision and accuracy results were within the acceptable limits. A very short run time of 1 min made it possible to analyze more than 500 human plasma samples per day. A very low quantification limit of SF allowed the applicability of the developed method for determination of SF in a bioequivalence study in human volunteers. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Analytical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562, Cairo, Egypt.
authors.forename: Mamdouh R
authors.initials: MR
authors.lastname: Rezk
authors.affiliation: Pharmaceutics and Industrial Pharmacy Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, 11562, Cairo, Egypt.
authors.forename: Emad B
authors.initials: EB
authors.lastname: Basalious
authors.affiliation: Advanced Research Center, Nasr City, Cairo, Egypt.
authors.forename: Mohammed E
authors.initials: ME
authors.lastname: Amin
mesh_terms: D000998:Antiviral Agents / Q000097:blood* / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D057230:Limit of Detection; D015203:Reproducibility of Results; D000069474:Sofosbuvir / Q000097:blood* / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency
chemical_list: D000998:Antiviral Agents; D000069474:Sofosbuvir
keywords: UPLC-MS/MS; bioequivalence; plasma; sofosbuvir; validation