Excretion of [{sup 3}H] chidamide in rats

Objective: To study the excretion of [{sup 3}H] chidamide by Sample Oxidizer pretreatment technology and to deduce the metabolites of chidamide in rats by isotopelabled technology. Methods: {sup 3}H-Labeled chidamide was used to study urine, feces and bile excretion (chemical dose 1.2 mg/kg, radioactive dose 1.24 mCi/kg) of chidamide after single intra- gastric dosing. Sample Oxidizer was utilized to deal with feces, urine and bile samples. The radioactivity was determined in Beckman 6500 liquid scintillation counter. Results: Methodology validation research showed that recovery of 3 H of the radionuclide in feces, urine and bile samples was about 100% and both the precision and accuracy were less than 10%. Tile cumulative radioactivity contents excreted in rat urine and feces were (18.77{+-}3.21)% and (63.28{+-}12.40)% within 336 h. The cumulative radioactivity content excreted in rat bile was (4.28{+-}2.72)% within 48 h. The total drug excretion rate in feces and urine were (82.25{+-}13.15)%. Meanwhile, there were radioactive metabolite peaks on the HPLC chromatograms. The radioactive level of intact drug was about 50% on the chromatogram. Conclusion: The proposed method using Sample Oxidizer pretreatment of feces, urine and bile samples for determining [{sup 3}H] chidamide is simple, accurate and precise. The metabolites of [{sup 3}H] chidamide were found in plasma, feces, urine and bile of rats after intragastric administration of [{sup 3}H] chidamide. About 50% of intact drug was excreted from rats body. (authors)