title: Identification of an isomer impurity in piperaquine drug substance.
abstract: A significant contaminant of the antimalarial drug piperaquine (1,3-bis-[4-(7-chloroquinolyl-4)-piperazinyl-1]propane) has been identified using liquid chromatography-mass spectrometry (LC-MS) and 2D NMR spectroscopy (1H-1H COSY, 1H-13C HSQC, 1H-13C HMBC). The impurity was identified as the positional isomer 1-[(5-chloroquinolin-4)-piperazinyl]-3-[(7-chloroquinolin-4)-piperazinyl]propane. The impurity is formed because of contamination of batches of 4,7-dichloroquinoline (a precursor in the synthesis of piperaquine) with 4,5-dichloroquinoline. The amount of impurity (peak area impurity/peak area piperaquine using LC-UV at 347 nm) in old batches of piperaquine and in Artekin (the combination of dihydroartemisinin-piperaquine) ranged from 1.5 to 5%.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand. niklas@tropmedres.ac
authors.forename: N
authors.initials: N
authors.lastname: Lindegårdh
authors.forename: F
authors.initials: F
authors.lastname: Giorgi
authors.forename: B
authors.initials: B
authors.lastname: Galletti
authors.forename: M
authors.initials: M
authors.lastname: Di Mattia
authors.forename: M
authors.initials: M
authors.lastname: Quaglia
authors.forename: D
authors.initials: D
authors.lastname: Carnevale
authors.forename: N J
authors.initials: NJ
authors.lastname: White
authors.forename: A
authors.initials: A
authors.lastname: Mazzanti
authors.forename: N P J
authors.initials: NP
authors.lastname: Day
mesh_terms: D000962:Antimalarials / Q000737:chemistry*; D002853:Chromatography, Liquid; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D011804:Quinolines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D010879:Piperazines
chemical_list: D000962:Antimalarials; D011804:Quinolines; C034759:piperaquine; D010879:Piperazines