Publication: Characterization of human urinary metabolites of the antimalarial piperaquine
Issued Date
2006-12-01
Resource Type
ISSN
1521009X
00909556
00909556
Other identifier(s)
2-s2.0-33751549060
Rights
Mahidol University
Rights Holder(s)
SCOPUS
Bibliographic Citation
Drug Metabolism and Disposition. Vol.34, No.12 (2006), 2011-2019
Suggested Citation
J. Tarning, Y. Bergqvist, N. P. Day, J. Bergquist, B. Arvidsson, N. J. White, M. Ashton, N. Lindegårdh Characterization of human urinary metabolites of the antimalarial piperaquine. Drug Metabolism and Disposition. Vol.34, No.12 (2006), 2011-2019. doi:10.1124/dmd.106.011494 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/23897
Research Projects
Organizational Units
Authors
Journal Issue
Thesis
Title
Characterization of human urinary metabolites of the antimalarial piperaquine
Abstract
Five metabolites of the antimalarial piperaquine (PQ) (1,3-bis-[4-(7- chloroquinolyl-4)-piperazinyl-1]-propane) have been identified and their molecular structures characterized. After a p.o. dose of dihydroartemisinin- piperaquine, urine collected over 16 h from two healthy subjects was analyzed using liquid chromatography (LC)/UV, LC/tandem mass spectrometry (MS/MS), Fourier transform ion cyclotron resonance (FTICR)/MS, and H NMR. Five different peaks were recognized as possible metabolites [M1, 320 m/z; M2, M3, and M4, 551 m/z (PQ + 16 m/z); and M5, 567 m/z (PQ + 32 m/z)] using LC/MS/MS with gradient elution. The proposed carboxylic M1 has a theoretical monoisotopic molecular mass of 320.1166 m/z, which is in accordance with the FTICR/MS (320.1168 m/z) findings. The LC/MS/MS results also showed a 551 m/z metabolite (M2) with a distinct difference both in polarity and fragmentation pattern compared with PQ, 7-hydroxypiperaquine, and the other 551 m/z metabolites. We suggest that this is caused by N-oxidation of PQ. The results showed two metabolites (M3 and M4) with a molecular ion at 551 m/z and similar fragmentation pattern as both PQ and 7-hydroxypiperaquine; therefore, they are likely to be hydroxylated PQ metabolites. The molecular structures of M1 and M2 were also confirmed using H NMR. Urinary excretion rate in one subject suggested a terminal elimination half-life of about 53 days for M1. Assuming formation rate-limiting kinetics, this would support recent findings that the terminal elimination half-life of PQ has been underestimated previously. Copyright © 2006 by The American Society for Pharmacology and Experimental Therapeutics.