PT - JOURNAL ARTICLE AU - Cheng Xiang AU - Xue Qiao AU - Qing Wang AU - Rui Li AU - Wenjuan Miao AU - Dean Guo AU - Min Ye TI - From Single Compounds to Herbal Extract: a Strategy to Systematically Characterize the Metabolites of Licorice in Rats AID - 10.1124/dmd.111.038695 DP - 2011 Jun 06 TA - Drug Metabolism and Disposition PG - dmd.111.038695 4099 - http://dmd.aspetjournals.org/content/early/2011/06/06/dmd.111.038695.short 4100 - http://dmd.aspetjournals.org/content/early/2011/06/06/dmd.111.038695.full AB - Due to 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 bio-samples 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. Firstly, ten representative compounds of licorice were administered to rats separately. A total of 68 metabolites were characterized by HPLC/DAD/ESI-MSn and LC/qTOF-MS analyses, together with enzyme hydrolysis. Among them, 13 compounds were confirmed by comparison with reference standards, including the 10 administered licorice compounds. Secondly, a high dosage (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/SRM-MS method when licorice water decoction was orally administered to rats at a clinical dosage (0.9 g crude drug per kilogram). 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.