Joshua F Emory1, Lauren A Seserko1, Mark A Marzinke2. 1. Department of Medicine, Johns Hopkins University, 600N. Wolfe St., Osler 500, Baltimore, MD 21287, United States. 2. 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.
Abstract
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.
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.
Authors: Samantha Abel; Deborah Russell; Lyndsey A Whitlock; Caroline E Ridgway; Angus N R Nedderman; Donald K Walker Journal: Br J Clin Pharmacol Date: 2008-04 Impact factor: 4.335
Authors: Samantha Abel; Elna van der Ryst; Maria C Rosario; Caroline E Ridgway; Christine G Medhurst; Richard J Taylor-Worth; Gary J Muirhead Journal: Br J Clin Pharmacol Date: 2008-04 Impact factor: 4.335
Authors: Don K Walker; Samantha Abel; Pierre Comby; Gary J Muirhead; Angus N R Nedderman; Dennis A Smith Journal: Drug Metab Dispos Date: 2005-01-13 Impact factor: 3.922
Authors: Roy M Gulick; Jacob Lalezari; James Goodrich; Nathan Clumeck; Edwin DeJesus; Andrzej Horban; Jeffrey Nadler; Bonaventura Clotet; Anders Karlsson; Michael Wohlfeiler; John B Montana; Mary McHale; John Sullivan; Caroline Ridgway; Steve Felstead; Michael W Dunne; Elna van der Ryst; Howard Mayer Journal: N Engl J Med Date: 2008-10-02 Impact factor: 91.245
Authors: Antonio D'Avolio; Marco Simiele; Lorena Baietto; Marco Siccardi; Mauro Sciandra; Samantha Patanella; Stefano Bonora; Giovanni Di Perri Journal: Ther Drug Monit Date: 2010-02 Impact factor: 3.681
Authors: A Fayet; A Béguin; B Zanolari; S Cruchon; N Guignard; A Telenti; M Cavassini; H F Günthard; T Buclin; J Biollaz; B Rochat; L A Decosterd Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2009-02-28 Impact factor: 3.205
Authors: Gerd Fätkenheuer; Mark Nelson; Adriano Lazzarin; Irina Konourina; Andy I M Hoepelman; Harry Lampiris; Bernard Hirschel; Pablo Tebas; François Raffi; Benoit Trottier; Nicholaos Bellos; Michael Saag; David A Cooper; Mike Westby; Margaret Tawadrous; John F Sullivan; Caroline Ridgway; Michael W Dunne; Steve Felstead; Howard Mayer; Elna van der Ryst Journal: N Engl J Med Date: 2008-10-02 Impact factor: 176.079
Authors: Anna K Blakney; Yonghou Jiang; Dale Whittington; Kim A Woodrow Journal: J Chromatogr B Analyt Technol Biomed Life Sci Date: 2016-05-02 Impact factor: 3.205
Authors: Ian M McGowan; Sylvain Chawki; Craig W Hendrix; Peter A Anton; Mark A Marzinke; Rhonda M Brand; Jarret C Engstrom; Lisa C Rohan; Kaleab Z Abebe; Nicola Richardson-Harman; Aaron Siegel; Alex Reinhart; John Steytler; Ronald Stall; Hans Spiegel; Beatrice Chen; Sharon L Achilles; Cindy E Jacobson; Elena Khanukova; Ross D Cranston Journal: AIDS Res Hum Retroviruses Date: 2021-09-14 Impact factor: 1.723
Authors: Todd T Brown; Krista Yuhas; Kenneth H Mayer; Raphael J Landovitz; Mark A Marzinke; Craig W Hendrix; Ying Q Chen; Karen L Klingman; Wairimu Chege; Marybeth B Mccauley; Roy M Gulick; Timothy J Wilkin Journal: J Antimicrob Chemother Date: 2022-02-02 Impact factor: 5.758
Authors: Teresa L Parsons; Joshua F Emory; Lauren A Seserko; Wutyi S Aung; Mark A Marzinke Journal: J Pharm Biomed Anal Date: 2014-06-21 Impact factor: 3.935
Authors: Roy M Gulick; Timothy J Wilkin; Ying Q Chen; Raphael J Landovitz; K Rivet Amico; Alicia M Young; Paul Richardson; Mark A Marzinke; Craig W Hendrix; Susan H Eshleman; Ian McGowan; Leslie M Cottle; Adriana Andrade; Cheryl Marcus; Karin L Klingman; Wairimu Chege; Alex R Rinehart; James F Rooney; Philip Andrew; Robert A Salata; Manya Magnus; Jason E Farley; Albert Liu; Ian Frank; Ken Ho; Jorge Santana; Joanne D Stekler; Marybeth McCauley; Kenneth H Mayer Journal: J Infect Dis Date: 2017-01-15 Impact factor: 5.226
Authors: Roy M Gulick; Timothy J Wilkin; Ying Q Chen; Raphael J Landovitz; K Rivet Amico; Alicia M Young; Paul Richardson; Mark A Marzinke; Craig W Hendrix; Susan H Eshleman; Ian McGowan; Leslie M Cottle; Adriana Andrade; Cheryl Marcus; Karin L Klingman; Wairimu Chege; Alex R Rinehart; James F Rooney; Philip Andrew; Robert A Salata; Marc Siegel; Yukari C Manabe; Ian Frank; Ken Ho; Jorge Santana; Joanne D Stekler; Shobha Swaminathan; Marybeth McCauley; Sally Hodder; Kenneth H Mayer Journal: Ann Intern Med Date: 2017-08-22 Impact factor: 25.391
Authors: Charlene S Dezzutti; Nicola Richardson-Harman; Lisa C Rohan; Mark A Marzinke; Craig J Hoesley; Lori Panther; Sherri Johnson; Jeremy P Nuttall; Annalene Nel; Beatrice A Chen Journal: Medicine (Baltimore) Date: 2016-07 Impact factor: 1.889