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Icariin is one of the predominant flavonoids contained in Herba Epimedii (Yin-yang-huo in Chinese), a well-known Chinese medicine for the treatment of cancers and immune system diseases. Although Herba Epimedii has been widely used in China and there are so many and various research reports on the herbal drug and its main flavones, very limited data is available on the tissue distribution and biotransformation of icariin. In the present study, a liquid chromatographic method combined with electrospray ionization tandem mass spectrometry was developed to quantify the concentration of icariin in rat plasma and various tissues collected at different time points after oral administration of the total flavonoid extract of Herba Epimedii at a dose of 0.69 g/kg (corresponding to 42 mg/g icariin). Biological samples were processed by simple protein precipitation. Genistein was chosen as internal standard. The method was successfully applied to plasma pharmacokinetic and tissue distribution studies of icariin in rat. As a result, it was worth noting that the tissue distribution characteristics of icariin exhibited a significant gender difference. Moreover,  in vivo  metabolism of icariin was also investigated. A total of 11 potential metabolites were found in rat feces collected in different time periods after oral and intramuscular administration of icariin.  In vivo  metabolic pathways were involved in hydrolysis, demethylation, oxidation, and conjugation. The preclinical data would be useful for fully understanding  in vivo  disposition of this compound and interpreting the mechanism of its biological response.

Pharmacokinetics, Tissue Distribution, and Metabolism Study of Icariin in Rat