Identification of an isomer impurity in piperaquine drug substance.
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%.
Lindegårdh
N
N
Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand. niklas@tropmedres.ac
Giorgi
F
F
Galletti
B
B
Di Mattia
M
M
Quaglia
M
M
Carnevale
D
D
White
N J
NJ
Mazzanti
A
A
Day
N P J
NP
D000962:Antimalarials / Q000737:chemistry*; D002853:Chromatography, Liquid; D007536:Isomerism; D009682:Magnetic Resonance Spectroscopy; D011804:Quinolines / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D010879:Piperazines
D000962:Antimalarials; D011804:Quinolines; C034759:piperaquine; D010879:Piperazines