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Determination of antimalarial compound, ARB-89 (7β-hydroxy-artemisinin carbamate) in rat serum by UPLC/MS/MS and its application in pharmacokinetics
Published in
2012
PMID: 22365535
Volume: 889-890
   
Pages: 123 - 129
Abstract
Among all the antimalarial agents, artemisinin and its semi synthetic family of analogs are the most potent antimalarials available for the treatment of Plasmodium falciparum infections. But these analogs have a few issues such as shorter half-lives and low oral bioavailability values. In order to overcome these inherent problems, novel artemisinin analogs were synthesized from 7β-hydroxy artemisinin by the Department of Medicinal Chemistry, University of Mississippi using a new synthesis mechanism. Out of all the 7β-hydroxy artemisinin analogs synthesized, 7β-hydroxy artemisinin carbamate (ARB-89) was chosen as a lead compound because of its high in vitro and in vivo activity. In this manuscript, a sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS) method was developed and validated for the quantification of ARB-89 in rat serum. The analysis was carried out on an Acquity™ UPLC BEH C 18 column (1.7μm, 2.1mm×50mm) with a flow rate of 0.3mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer in positive electrospray ionization (ESI) mode. The selected mass-to-charge (m/z) ratio transitions used in the multiple reaction monitoring (MRM) for ARB-89 and artemisinin (internal standard) were m/z 778.4>253.4 and m/z 283.4>151.1 respectively. The calibration curve was linear from 1.00ng/mL to 10.0μg/mL (r 2=0.999). A simple protein precipitation method was used for extraction. Moreover, the inter-day and intra-day precision values were found to be less than 15%. The recoveries of the method ranged from 94.0% to 96.7% at three concentrations. ARB-89 in rat serum was found to be stable at room temperature for 12h. This method was successfully used to quantitate the novel antimalarial compound ARB-89 after intravenous and oral administration to rats. © 2012 Elsevier B.V.
About the journal
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
ISSN15700232
Open AccessNo
Concepts (53)
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    ANTIMALARIAL
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    Artemisinin
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    Bioavailability
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    RAT SERUM
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    UPLC/MS/MS
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    Biochemistry
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    Body fluids
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    Electrospray ionization
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    Liquid chromatography
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    Mass spectrometry
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    Pharmacokinetics
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    Precipitation (chemical)
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    Rats
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    Lead compounds
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    7BETA HYDROXY ARTEMISININ CARBAMATE
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    Antimalarial agent
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    ARB 89
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    Unclassified drug
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    Animal experiment
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    Area under the curve
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    Article
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    Blood analysis
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    DISTRIBUTION VOLUME
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    Drug blood level
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    DRUG CLEARANCE
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    Drug determination
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    Drug formulation
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    Drug half life
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    Drug stability
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    Electrospray mass spectrometry
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    Flow rate
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    Male
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    MAXIMUM PLASMA CONCENTRATION
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    Molecular weight
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    Nonhuman
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    Priority journal
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    Quadrupole mass spectrometry
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    Rat
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    Room temperature
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    Tandem mass spectrometry
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    TIME TO MAXIMUM PLASMA CONCENTRATION
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    ULTRA PERFORMANCE LIQUID CHROMATOGRAPHY
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    Animals
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    Antimalarials
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    ARTEMISININS
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    Carbamates
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    Chromatography, high pressure liquid
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    Linear models
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    Rats, sprague-dawley
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    Reproducibility of results
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    Sensitivity and specificity
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    Plasmodium falciparum
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    Rattus