An LC-MS-MS method for quantitative determination of maraviroc (UK-427,857) in human plasma, urine and cerebrospinal fluid

✍ Scribed by Ed Brewer; Tonya Felix; Phil Clarke; Alan Edgington; David Muirhead

• Publisher: John Wiley and Sons
• Year: 2010
• Tongue: English
• Weight: 543 KB
• Volume: 24
• Category: Article
• ISSN: 0269-3879
• DOI: 10.1002/bmc.1442

✦ Synopsis

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. Copyright © 2010 John Wiley & Sons, Ltd.