Structural characterization of the oxidative degradation products of an antifungal agent SCH 56592 by LC-NMR and LC-MS.
LC-NMR and LC-MS were used to characterize the structures of four major degradation products of SCH 56592, an antifungal drug candidate in clinical trials. These compounds were formed under stress conditions in which the bulk drug substance was heated in air at 150 degrees C for 12 days, and were separated from SCH 56592 as a mixture using a semi-preparative HPLC method. The data from LC-NMR, LC-ESI-MS (electrospray ionization mass spectrometry) and LC-ESI-MS/MS indicate that the oxidation occurred at the piperazine ring in the center of the drug molecule. The structures of the degradation products were determined from the 1H NMR spectra obtained via LC-NMR, which were supported by LC-ESI-MS and LC-ESI-MS/MS analyses. A novel degradation pathway of SCH 56592 was proposed based on these characterized structures.
Feng
W
W
Schering-Plough Research Institute, Mail Stop: K-15-0450, 2015, Galloping Hill Road, 07033, Kenilworth, NJ, USA
Liu
H
H
Chen
G
G
Malchow
R
R
Bennett
F
F
Lin
E
E
Pramanik
B
B
Chan
T M
TM
D000935:Antifungal Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D014230:Triazoles / Q000737:chemistry*
D000935:Antifungal Agents; D014230:Triazoles; C101425:posaconazole