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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/23897
Title: Characterization of human urinary metabolites of the antimalarial piperaquine
Authors: J. Tarning
Y. Bergqvist
N. P. Day
J. Bergquist
B. Arvidsson
N. J. White
M. Ashton
N. Lindegårdh
Goteborg University, Sahlgrenska Academy
Hogskolan Dalarna
Mahidol University
Nuffield Department of Clinical Medicine
Uppsala Universitet
Keywords: Pharmacology, Toxicology and Pharmaceutics
Issue Date: 1-Dec-2006
Citation: Drug Metabolism and Disposition. Vol.34, No.12 (2006), 2011-2019
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.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=33751549060&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/23897
ISSN: 1521009X
00909556
Appears in Collections:Scopus 2006-2010

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