title: Identification and characterization of process related impurities in chloroquine and hydroxychloroquine by LC/IT/MS, LC/TOF/MS and NMR.
abstract: The focus of this study is identification and characterization of major unknown impurities in chloroquine (CQ) and hydroxychloroquine (HCQ) bulk drug samples using liquid chromatography/ion trap mass spectrometry (LC/IT/MS) and liquid chromatography/time of flight mass spectrometry (LC/TOF/MS). The newly developed LC/MS method was employed for the analysis of both the drugs. The analysis revealed the presence of two impurities in each of the drugs. The impurities are designated as CQ-I, CQ-II (for chloroquine); HCQ-I and HCQ-II (for hydroxychloroquine). Three of the impurities, CQ-II, HCQ-I and HCQ-II were unknown have not been reported previously. Accurate masses of the impurities were determined by using Q-TOF mass spectrometer and fragmentation behavior was studied by an ion trap mass spectrometer. Based on the spectrometric data and synthetic specifics the structures of CQ-II, HCQ-I and HCQ-II were proposed as 1,4 pentanediamine, N(4)(7-chloro-4-quinolinyl), N(4)-chloromethyl, N(4)-ethylamine; 2-(4-(7-chloroquinolin-4-ylamino) pentylamino) ethanol and [[4-[(7-chloro-4-quinolyl) amino] N-pentyl] N-chloromethyl-N-ethylamino] ethanol respectively. The impurities were isolated by semi-preparative HPLC and structures were confirmed by NMR spectroscopy. The formation and through characterization of known CQ-I impurity is also discussed.
authors.affiliation: Department of Chemistry, University of Mumbai, Vidyanagari, Kalina, Santacruz (E), Mumbai, India. dongrevg@yahoo.com
authors.forename: Vaijanath G
authors.initials: VG
authors.lastname: Dongre
authors.forename: Pradeep D
authors.initials: PD
authors.lastname: Ghugare
authors.forename: Pravin
authors.initials: P
authors.lastname: Karmuse
authors.forename: Dharmendra
authors.initials: D
authors.lastname: Singh
authors.forename: Atul
authors.initials: A
authors.lastname: Jadhav
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000962:Antimalarials / Q000032:analysis*; D002738:Chloroquine / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D006886:Hydroxychloroquine / Q000032:analysis*; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000962:Antimalarials; D007202:Indicators and Reagents; D006886:Hydroxychloroquine; D002738:Chloroquine