Investigation of amodiaquine bulk drug impurities by liquid chromatography/ion trap mass spectrometry.
Three unknown impurities in an amodiaquine bulk drug sample were detected by reversed-phase high-performance liquid chromatography with ultraviolet detection (HPLC/UV). A liquid chromatography/tandem mass spectrometry (LC/MS(n)) method is described for the investigation of these impurities. Mass spectral data were acquired on an LCQ ion trap mass analyzer equipped with an electrospray ionization (ESI) source operated in positive ion mode. The fragmentation behavior of amodiaquine and its impurities has been studied. Based on the mass spectral data and the specifics of the synthetic route, the possible structures of these impurities were elucidated as 4-[(5-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol (impurity I), 4-[(7-chloroquinolin-4-yl)-amino]phenol (impurity II) and 4-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)-N(1)-oxy]phenol (impurity III). The structures were confirmed by their independent synthesis and NMR spectral assignment.
Department of Chemistry, University of Mumbai, Santacruz East, Mumbai, India. dongrevg@yahoo.com
Vaijanath G
VG
Dongre
Pravin P
PP
Karmuse
Pradip D
PD
Ghugare
Sunil K
SK
Kanojiya
Sadanand
S
Rawal
D000655:Amodiaquine / Q000138:chemical synthesis / Q000737:chemistry*; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry*; D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination / Q000517:prevention & control*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D013056:Spectrophotometry, Ultraviolet
D000962:Antimalarials; D000655:Amodiaquine