title: Development and application of a simple LC-MS method for the determination of plasma maraviroc concentrations.
abstract: Maraviroc is an orally available antagonist of the CCR5 chemokine receptor, which acts as a human immunodeficiency virus type 1 (HIV-1) coreceptor. Binding of maraviroc to this receptor blocks HIV-1 attachment to the coreceptor and prevents HIV-1 from entering host cells. Maraviroc does not require intracellular processing to exert this activity. Drug interaction studies have shown changes in maraviroc exposure when given with other anti-HIV medications, and thus quantification of maraviroc in human plasma is important to manage drug interactions and to evaluate the relationship between plasma concentrations and treatment response. We developed a conventional LC-MS method for determining plasma maraviroc concentrations, validated by estimating precision and accuracy for inter- and intraday analysis in the concentration range of 0.011-2.188 µg/ml. The calibration curve was linear within this range. The average accuracy ranged from 92.7% to 99.7%, while the relative standard deviations of both inter- and intraday assays were less than 7.1%. Recovery of maraviroc exceeded 86.7%. Our LC-MS method provides a conventional, accurate and precise way to determine the maraviroc concentration in human plasma. This method enables dose adjustment based on monitoring plasma maraviroc concentrations and permits management of drug interactions and toxicity.
authors.affiliation: Department of Pharmacy, National Hospital Organization Nagoya Medical Center, Aichi, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Takahashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hirano
authors.forename: Nami
authors.initials: N
authors.lastname: Okubo
authors.forename: Eri
authors.initials: E
authors.lastname: Kinoshita
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Nomura
authors.forename: Tsuguhiro
authors.initials: T
authors.lastname: Kaneda
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood*; D023241:Antiretroviral Therapy, Highly Active; D001774:Blood Chemical Analysis / Q000379:methods*; D065100:CCR5 Receptor Antagonists; D002853:Chromatography, Liquid / Q000379:methods; D003510:Cyclohexanes / Q000008:administration & dosage / Q000097:blood*; D016903:Drug Monitoring; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D015497:HIV-1 / Q000187:drug effects; D006801:Humans; D008297:Male; D000077592:Maraviroc; D013058:Mass Spectrometry / Q000379:methods; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood*
chemical_list: D019380:Anti-HIV Agents; D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc