title: A validated HPLC-MS method for quantification of the CCR5 inhibitor maraviroc in HIV+ human plasma.
abstract: Maraviroc is a CCR5 inhibitor approved in 2007 for treatment of therapy experienced adult patients infected with CCR5-tropic HIV-1 virus. International guidelines for HIV therapy indicate a plasma concentration cutoff of maraviroc for response. We developed and validated a new HPLC-MS method to quantify maraviroc concentrations in human plasma. 6,7-Dimethyl-2,3-di(2-pyridyl)quinoxaline was used as internal standard and added to 100μL of plasma. Samples were then treated with 500μL of acetonitrile for the protein precipitation procedure. An analytical T3 Atlantis column (150mm×4.6mm i.d.) with a particle size of 5μm was used to separate the compounds and ions were detected at m/z 257.5 and 313.3 for maraviroc and quinoxaline respectively. The calibration curve was linear up to 2500ng/mL. The mean recovery of maraviroc was 89.1%. All validation data results were in accordance to Food and Drug Administration and European Medicines Agency requirements. The HPLC-MS method reported here could be used routinely to monitor plasma concentrations of maraviroc in HIV-infected patients.
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Simiele
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Baietto
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Audino
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Sciandra
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Bonora
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Di Perri
authors.affiliation: Unit of Infectious Diseases, University of Turin, Department of Medical Sciences, Amedeo di Savoia Hospital, Turin, Italy. Electronic address: antonio.davolio@unito.it.
authors.forename: Antonio
authors.initials: A
authors.lastname: D'Avolio
mesh_terms: D065100:CCR5 Receptor Antagonists; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003510:Cyclohexanes / Q000097:blood* / Q000737:chemistry*; D015658:HIV Infections / Q000097:blood*; D006801:Humans; D057230:Limit of Detection; D000077592:Maraviroc; D013058:Mass Spectrometry / Q000379:methods; D019713:Receptors, CCR5; D012015:Reference Standards; D012680:Sensitivity and Specificity; D014230:Triazoles / Q000097:blood* / Q000737:chemistry*
chemical_list: D065100:CCR5 Receptor Antagonists; C584933:CCR5 protein, human; D003510:Cyclohexanes; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc
keywords: HIV; HPLC-MS; Maraviroc; Plasma; Therapeutic drug monitoring