title: 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.affiliation: Pharmaceutics, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, United States. justincchow@hotmail.com
authors.forename: Justin
authors.initials: J
authors.lastname: Chow
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Liu
authors.forename: Kate
authors.initials: K
authors.lastname: Comstock
authors.forename: Michael
authors.initials: M
authors.lastname: Brandl
authors.forename: Fangling
authors.initials: F
authors.lastname: Lin
authors.forename: Fujun
authors.initials: F
authors.lastname: Li
authors.forename: Keshab
authors.initials: K
authors.lastname: Sarma
authors.forename: Tom
authors.initials: T
authors.lastname: Alfredson
mesh_terms: D000998:Antiviral Agents / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000032:analysis; D004340:Drug Contamination; D004952:Esters / Q000032:analysis; D006526:Hepatitis C / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D012324:RNA-Dependent RNA Polymerase / Q000037:antagonists & inhibitors*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C552098:2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine; D000998:Antiviral Agents; D004952:Esters; D003841:Deoxycytidine; D012324:RNA-Dependent RNA Polymerase