title: Identification of four new degradation products of epirubicin through forced degradation, LC-UV, MSn and LC-MS-TOF studies.
abstract: Epirubicin (EPI) was subjected to International Conference on Harmonization recommended forced degradation under the conditions of hydrolysis, oxidation, dry heat and photolysis to characterize its possible impurities and/or degradation products. The drug was found highly unstable to alkaline hydrolysis even at room temperature, unstable to acid hydrolysis at 80°C and to oxidation at room temperature. The hydrolytic and oxidative degradation products were resolved on an Agilent RP8 (150 mm × 4.6 mm; 5 µm) column with isocratic elution using mobile phase composed of ammonium formate (10 mM, pH 3.0), acetonitrile and methanol. The drug degraded to four oxidative products (O-I, O-II, O-III and O-IV) and to one acid hydrolyzed product (A-I). Purity of each peak in liquid chromatography-ultraviolet (LC-UV) chromatogram was ascertained through photodiode array (LC-PDA) analysis. The products were characterized through electrospray ionization-mass spectrometry (+ESI-MS(n)) studies on EPI and liquid chromatography-time of flight mass spectrometry (LC-MS-TOF) studies on degraded drug solutions. The products, O-I-O-IV, were characterized as 2-hydroxy-8-desacetylepirubicin-8-hydroperoxide, 4-hydroxy-8-desacetylepirubicin-8-hydroperoxide, 8-desacetylepirubicin-8-hydroperoxide and 8-desacetylepirubicin, respectively, and product A-I was characterized as deglucosaminylepirubicin. While A-I was found to be a pharmacopoeial impurity, all oxidative products were found to be new degradation impurities. The mechanisms and pathways of degradation of EPI were discussed and outlined.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Kaushik
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Balraj
authors.initials: B
authors.lastname: Saini
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India gulshanbansal@rediffmail.com gulshanbansal@gmail.com.
authors.forename: Gulshan
authors.initials: G
authors.lastname: Bansal
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D015251:Epirubicin / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
chemical_list: D000903:Antibiotics, Antineoplastic; D015251:Epirubicin