RT Journal Article
SR Electronic
T1 From Single Compounds to Herbal Extract: A Strategy to Systematically Characterize the Metabolites of Licorice in Rats
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1597
OP 1608
DO 10.1124/dmd.111.038695
VO 39
IS 9
A1 Cheng Xiang
A1 Xue Qiao
A1 Qing Wang
A1 Rui Li
A1 Wenjuan Miao
A1 Dean Guo
A1 Min Ye
YR 2011
UL http://dmd.aspetjournals.org/content/39/9/1597.abstract
AB 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.