title: An LC-MS-MS method for quantitative determination of maraviroc (UK-427,857) in human plasma, urine and cerebrospinal fluid.
abstract: Maraviroc is a first-in-class CCR5 antagonist that shows potent anti-HIV-1 activity in vitro and in vivo and is well tolerated in both healthy volunteers and HIV-1-infected patients. The method for determination of maraviroc (UK-427,857) and its major metabolite (UK-408,027) in human plasma consists of a protein-precipitation procedure and analysis by liquid chromatography/tandem mass spectrometry using positive ion TurboIonSpray® ionization and multiple reaction monitoring. The assay has been validated over a concentration range of 0.500-500 ng/mL for both analytes. The determinations of maraviroc in human cerebrospinal fluid (0.500-500 ng/mL) and in urine (5.00-5000 ng/mL) have also been validated but do not include measurement of the metabolite. The validations included extraction recovery, intra-assay and inter-assay precision and accuracy, stability of stock and spiking solutions, freeze-thaw stability, matrix stability, processed-extract stability, and evaluation of potential interferences from selected medications in plasma or urine.
authors.affiliation: Tandem Laboratories, 115 Silvia Street, West Trenton, NJ 08628, USA. Ed.Brewer@tandemlabs.com
authors.forename: Ed
authors.initials: E
authors.lastname: Brewer
authors.forename: Tonya
authors.initials: T
authors.lastname: Felix
authors.forename: Phil
authors.initials: P
authors.lastname: Clarke
authors.forename: Alan
authors.initials: A
authors.lastname: Edgington
authors.forename: David
authors.initials: D
authors.lastname: Muirhead
mesh_terms: D019380:Anti-HIV Agents / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003510:Cyclohexanes / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine; D006801:Humans; D000077592:Maraviroc; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000032:analysis* / Q000097:blood / Q000134:cerebrospinal fluid / Q000652:urine
chemical_list: D019380:Anti-HIV Agents; D003510:Cyclohexanes; D014230:Triazoles; D000077592:Maraviroc