Characterization of degradation products of idarubicin through LC-UV, MS(n) and LC-MS-TOF studies.
Idarubicin was subjected to forced degradation under the ICH recommended conditions of hydrolysis, oxidation, dry heat and photolysis to characterize its possible impurities and/or degradation products. The drug was found unstable to acid hydrolysis at 85°C and to alkaline hydrolysis, and oxidation at room temperature. The hydrolytic and oxidative degradation products were resolved with gradient and isocratic elution, respectively on an Inertsil RP18 (250 mm × 4.6mm; 5 μ) column with HCOONH4 (20mM, pH 3.0) and acetonitrile. The drug degraded to two products (O-I and O-II) in oxidative condition, two products (K-I and K-II) in alkaline hydrolytic, and one product (A-I) in acidic hydrolytic conditions. The purity of each in the LC-UV chromatogram was ascertained through LC-PDA analysis. The products were characterized through +ESI-MS(n) studies on the drug and LC-MS-TOF studies on the degraded drug solutions. Based on the multistage mass fragmentation pattern of idarubicin and accurate mass analysis of the degradation products, the O-I, O-II and A-I were characterized as desacetylidarubicin hydroperoxide, desacetylidarubicin and deglucosaminylidarubicin, respectively. The products K-I and K-II were not characterized due to their low concentrations and/or extremely weak ionization. The mechanisms of degradation of idarubicin to these products were proposed and discussed.
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Dheeraj
D
Kaushik
Gulshan
G
Bansal
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D006868:Hydrolysis; D015255:Idarubicin / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet
D015255:Idarubicin
Degradation product; Forced degradation; Idarubicin; LC-MS-TOF; Mass fragmentation