Isolation and identification of ester impurities in RG7128, an HCV polymerase inhibitor.
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.
Chow
Justin
J
Pharmaceutics, Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, United States. justincchow@hotmail.com
Liu
Yanzhou
Y
Comstock
Kate
K
Brandl
Michael
M
Lin
Fangling
F
Li
Fujun
F
Sarma
Keshab
K
Alfredson
Tom
T
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
C552098:2'-fluoro-2'-methyl-3',5'-diisobutyryldeoxycytidine; D000998:Antiviral Agents; D004952:Esters; D003841:Deoxycytidine; D012324:RNA-Dependent RNA Polymerase