Isolation and identification of ester impurities in RG7128, an HCV polymerase inhibitor.

Abstract

RG7128 is a di-ester prodrug of a cytidine analog for the treatment of hepatitis C virus (HCV) infection. The structures of nine low level impurities (0.05-0.10%) in RG7128 drug substance were elucidated. The majority of the impurities were formed during the synthesis of the prodrug from the parent drug. Structural elucidations of the impurities were achieved either by enrichment of the impurities using preparative chromatography followed by spectroscopic techniques or by confirmation with a reference sample. Heart-cut and recycle chromatographic techniques were applied to purify closely eluting isomers of RG7128.

• Authors: Justin Chow, Yanzhou Liu, Kate Comstock, Michael Brandl, Fangling Lin, Fujun Li, Keshab Sarma, Tom Alfredson
• Journal: Journal of pharmaceutical and biomedical analysis (J Pharm Biomed Anal) Vol. 53 Issue 3 Pg. 710-6 (Nov 02 2010) ISSN: 1873-264X [Electronic] England
• PMID: 20439144 (Publication Type: Journal Article)
• Copyright: Copyright (c) 2010 Elsevier B.V. All rights reserved.

Chemical References

• 2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine
• Antiviral Agents
• Esters
• Deoxycytidine
• RNA-Dependent RNA Polymerase

Topics

• Antiviral Agents (analysis)
• Chromatography, High Pressure Liquid
• Deoxycytidine (analogs & derivatives, analysis)
• Drug Contamination
• Esters (analysis)
• Hepatitis C (drug therapy)
• Magnetic Resonance Spectroscopy
• RNA-Dependent RNA Polymerase (antagonists & inhibitors)
• Spectrometry, Mass, Electrospray Ionization