Dynamic Biodistribution of Icaritin and Its Phase-II Metabolite in Rat Tissues by Ultra-High Performance Liquid Chromatography-Tandem Mass Spectrometry.

Icaritin (ICT), a major component in herb Epimedium brevicornum Maxim., shows beneficial effects for the treatment of osteoporosis and various cancers, and is predominantly metabolized to glucuronidated icaritin (GICT). Although clinical trials of ICT have exhibited good safety and tolerance, the dynamic bioditributions of ICT and GICT have not been reported. In the present study, the chemical structure of GICT was firstly reported, and a reliable ultra-high performance liquid chromatography-tandem mass spectrometry method (UHPLC-MS/MS) was firstly established for the simultaneous quantifications of ICT and GICT in rat tissues. The dynamic distribution of ICT and GICT in rat tissues and their pharmacokinetic parameters have been reported for the first time. ICT, GICT and the internal standard coumestrol were separated on a C18 column with a gradient mobile phase of acetonitrile and water containing ammonium formate and formic acid at a flow rate of 0.3 mL min(-1). The analytes were quantified by a triple quadrupole tandem mass spectrometer in the negative ionization mode. The lower limit of quantification values for ICT and GICT were 0.2 and 2 ng mL(-1), respectively. Good selectivity, linearity, accuracy, precision and recovery were achieved, and no significant matrix effect was observed. The UHPLC-MS/MS was firstly applied to a dynamic biodistribution study of ICT and GICT in rats, following an intraperitoneal administration of ICT at a dose of 10 mg kg(-1).