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Development and bioanalytical validation of a liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method for the quantification of the CCR5 antagonist maraviroc in human plasma.
Emory, Joshua F; Seserko, Lauren A; Marzinke, Mark A.
Afiliación
  • Emory JF; Department of Medicine, Johns Hopkins University, 600N. Wolfe St., Osler 500, Baltimore, MD 21287, United States.
  • Seserko LA; Department of Medicine, Johns Hopkins University, 600N. Wolfe St., Osler 500, Baltimore, MD 21287, United States.
  • Marzinke MA; Department of Medicine, Johns Hopkins University, 600N. Wolfe St., Osler 500, Baltimore, MD 21287, United States; Department of Pathology, Johns Hopkins University, 600N. Wolfe St., Osler 500, Baltimore, MD 21287, United States. Electronic address: mmarzin1@jhmi.edu.
Clin Chim Acta ; 431: 198-205, 2014 Apr 20.
Article en En | MEDLINE | ID: mdl-24561264
BACKGROUND: Maraviroc is a CCR5 antagonist that has been utilized as a viral entry inhibitor in the management of HIV-1. Current clinical trials are pursuing maraviroc drug efficacy in both oral and topical formulations. Therefore, in order to fully understand drug pharmacokinetics, a sensitive method is required to quantify plasma drug concentrations. METHODS: Maraviroc-spiked plasma was combined with acetonitrile containing an isotopically-labeled internal standard, and following protein precipitation, samples were evaporated to dryness and reconstituted for liquid chromatographic-tandem mass spectrometric (LC-MS/MS) analysis. Chromatographic separation was achieved on a Waters BEH C8, 50×2.1 mm UPLC column, with a 1.7 µm particle size and the eluent was analyzed using an API 4000 mass analyzer in selected reaction monitoring mode. The method was validated as per FDA Bioanalytical Method Validation guidelines. RESULTS: The analytical measuring range of the LC-MS/MS method is 0.5-1000 ng/ml. Calibration curves were generated using weighted 1/x(2) quadratic regression. Inter-and intra-assay precision was ≤5.38% and ≤5.98%, respectively; inter-and intra-assay accuracy (%DEV) was ≤10.2% and ≤8.44%, respectively. Additional studies illustrated similar matrix effects between maraviroc and its internal standard, and that maraviroc is stable under a variety of conditions. Method comparison studies with a reference LC-MS/MS method show a slope of 0.948 with a Spearman coefficient of 0.98. CONCLUSIONS: Based on the validation metrics, we have generated a sensitive and automated LC-MS/MS method for maraviroc quantification in human plasma.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazoles / Cromatografía Líquida de Alta Presión / Ciclohexanos / Inhibidores de Fusión de VIH / Espectrometría de Masas en Tándem / Antagonistas de los Receptores CCR5 Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: Clin Chim Acta Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Triazoles / Cromatografía Líquida de Alta Presión / Ciclohexanos / Inhibidores de Fusión de VIH / Espectrometría de Masas en Tándem / Antagonistas de los Receptores CCR5 Tipo de estudio: Guideline Límite: Humans Idioma: En Revista: Clin Chim Acta Año: 2014 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Países Bajos