Abstract
Because of the complicated chemical composition of traditional Chinese medicines (TCMs), their metabolic study has been a great challenge, especially when they are used in the traditional way, i.e., clinical oral dose of water decoction. Poor understanding of metabolic pathways and too low metabolite concentrations to be detected in biosamples are the major hurdles. In the present work, a three-step strategy was proposed to systematically characterize in vivo metabolites of TCMs at a normal clinical dosage. Licorice, one of the most popular TCMs, was studied as a model. First, 10 representative compounds of licorice were administered to rats separately. A total of 68 metabolites were characterized by high-performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry and liquid chromatography (LC)/quadrupole time-of-flight-mass spectrometry (MS) analyses, together with enzyme hydrolysis. Among these, 13 compounds were confirmed by comparison with reference standards, including the 10 administered licorice compounds. Second, a high dose (equivalent to 20-fold clinical dosage) of licorice water extract was administered, and 22 more metabolites were characterized. Finally, these metabolites (including constituents of licorice) were determined by a highly sensitive and selective LC/selected reaction monitoring-MS method when the licorice water decoction was orally administered to rats at a clinical dosage (0.9 g crude drug/kg). A total of 42 metabolites in plasma and 62 metabolites in urine were detected. This is the first attempt to fully profile the in vivo metabolites of licorice at a normal clinical dosage.
Footnotes
This work was supported by the 985 Project of Peking University [Grant 985-2-119-121]; and the National Science and Technology Mega Project for Primary Drug Innovation from the Ministry of Science and Technology of China [Grant 2009ZX09304-002].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.111.038695.
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The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
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ABBREVIATIONS:
- TCM
- traditional Chinese medicine
- LC
- liquid chromatography
- MS
- mass spectrometry
- SRM
- selected reaction monitoring
- LWE
- licorice water extract
- HPLC
- high-performance liquid chromatography
- LG
- liquiritigenin
- LQ
- liquiritin
- LA
- liquiritin apioside
- ILG
- isoliquiritigenin
- ILQ
- isoliquiritin
- ILA
- isoliquiritin apioside
- ONO
- ononin
- GLY
- glycyrrhizic acid
- DHF
- 7,4′-dihydroxyflavone
- IAA
- isoangustone A
- FOR
- formononetin
- DA
- davidigenin
- HPLC/DAD/ESI-MSn
- high-performance liquid chromatography coupled with diode-array detection and electrospray ionization tandem mass spectrometry
- qTOF-MS
- quadrupole time-of-flight mass spectrometry
- LCD
- licorice compounds database
- MS/MS
- tandem mass spectrometry
- GluA
- glucuronic acid.
- Received February 12, 2011.
- Accepted June 6, 2011.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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