Metabolism and Excretion of Kakkalide and Its Metabolites in Rat Urine, Bile, and Feces as Determined by HPLC/UV and LC/MS/MS

This study investigated the metabolic fate of kakkalide (irisolidone 7-xylosylglucoside), a major isoflavone found in extracts of Pueraria lobata flowers, and in rat urine, bile, and feces. Using HPLC/UV or LC/MS/MS methods, seven metabolites, tectorigenin-7-O-glucuronide, tectorigenin-7-O-sulfate, tectorigenin-4′-O-sulfate, 6-OH biochanin A-glucuronide, irisolidone-7-O-glucuronide, tectorigenin, and irisolidone were identified in rat urine after oral administration of kakkalide. Furthermore, irisolidone-7-O-glucuronide was found in bile, and irisolidone and kakkalide were found in feces. An HPLC/UV method for simultaneous quantification of all the metabolites and kakkalide in urine, bile, and feces was developed using daidzein or apigenin as the internal standard. Over a 72-h period, 13.2 ± 2.8 % of the kakkalide was excreted as seven metabolites in urine. Over the same time period, irisolidone-7-O-glucuronide excretion in bile accounted for 3.8 ± 1.1 % of the dose, while kakkalide and irisolidone excretion in feces accounted for 2.1 ± 0.7 % and 0.7 ± 0.1 % of the dose, respectively. The results indicate that urine is the primary route of kakkalide elimination in vivo and that extensive metabolism may be one of the reasons for the low bioavailability of kakkalide.