Oral absorption, distribution, metabolism, and excretion of icaritin in rats by Q‐TOF and UHPLC–MS/MS

Icaritin (ICT) displays numerous pharmacological activities for the treatment of various cancers, osteoporosis, inflammation, and angiocardiopathy. The absorption, distribution, metabolism, and excretion of ICT still remain unknown. ICT was administered to rats at 2 mg/kg for intravenous injection or 40 mg/kg for oral route. Major metabolite of ICT was identified using quadrupole time‐of‐flight (Q‐TOF), and ICT and its major metabolite were quantified in plasma, tissues, urine, faeces, and bile by ultra‐high performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS). A total of 24 metabolites of ICT in plasma were identified and mono C‐7 glucuronide glucuronidated icaritin (GICT) was the major metabolite of ICT after oral administration. The absolute bioavailability of ICT was 4.33% although ICT was rapidly absorbed into the blood. For oral administration, concentrations of GICT at various time points was 6.38–8.81‐fold higher than those of ICT, and the area under the curve (AUC) of GICT was about 8‐fold higher than that of ICT, while AUC values of ICT and GICT were almost equal for intravenous injection. Approximately 65.7% ICT and 42.7% GICT were distributed in liver and kidney, respectively. Unabsorbed ICT was mainly excreted as the parent form in faeces with at least 60% of administered dose during 24 h, whereas absorbed ICT was predominantly excreted as GICT from urine with 2.74% of administered dose accounting for 63.28% of absorbed drug. ICT was rapidly absorbed into the blood although a large amount of ICT remained unabsorbed, and then rapidly and mainly metabolized to GICT. ICT mainly distributed in liver, while GICT predominantly distributed in kidney. Absorbed ICT and GICT were predominantly excreted via urine, and unabsorbed ICT was mainly excreted as the parent form in faeces. Copyright © 2017 John Wiley & Sons, Ltd.