A Microbial Transformation Model for Simulating Mammal Metabolism of Artemisinin

Artemisinin (ART) is a highly effective antimalarial agent isolated from the traditional Chinese herb Qinghao. Metabolism of ART and its derivatives in the body is one of the most pressing issues for pharmaceutical scientists. Herein, an efficient in vitro microorganism model for simulation of metab...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2019-01, Vol.24 (2), p.315
Main Authors: Ma, Yue, Sun, Peng, Zhao, Yifan, Wang, Kun, Chang, Xiaoqiang, Bai, Yue, Zhang, Dong, Yang, Lan
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antimalarials - administration & dosage
Antimalarials - pharmacokinetics
Artemisinin
Artemisinins - administration & dosage
Artemisinins - analysis
Artemisinins - pharmacokinetics
Chromatography
Chromatography, High Pressure Liquid
Cunninghamella - chemistry
Cunninghamella - growth & development
Cunninghamella elegans
Dihydroartemisinin
Herbal medicine
Hydroxylation
identification
in vivo
Ionization
Liquid chromatography
Mammals
Mass spectrometry
Mass spectroscopy
Metabolism
metabolite
Metabolites
Metabolomics - methods
Mice
microbial transformation
Microorganisms
Molecular Structure
Plasma
Quadrupoles
Species Specificity
Spectrometry, Mass, Electrospray Ionization
UNIFI software
UPLC-ESI-Q-TOF-MSE
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Summary:Artemisinin (ART) is a highly effective antimalarial agent isolated from the traditional Chinese herb Qinghao. Metabolism of ART and its derivatives in the body is one of the most pressing issues for pharmaceutical scientists. Herein, an efficient in vitro microorganism model for simulation of metabolism of ART in vivo was developed employing Metabolites in the microbial transformation system and plasma of mice pre-administrated ART orally were analyzed by ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-quadrupole time-of-flight (Q-TOF)-mass spectrometry (MS ) combined with UNIFI software. Thirty-two metabolites were identified in vitro and 23 were identified in vivo. After comparison, 16 products were found to be common to both models including monohydroxylated ART, dihydroxylated ART, deoxyartemisinin, hydroxylated deoxyartemisinin, hydroxylated dihydroartemisinin (DHA), and hydroxylated deoxy-DHA. These results revealed that CICC 40250 functioned as an appropriate model to mimic ART metabolism in vivo. Moreover, an overall description of metabolites of ART from CICC 40250 has been provided. Notably, DHA was detected and identified as a metabolite of ART in mouse plasma for the first time.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules24020315