Abstract: AIM: To study chronopharmacokinetics of helicid and its metabolites. METHODS: An HPLC-MS method for simultaneous determination of helicid and its three phase I metabolites were established and validated. At 8∶00, 14∶00 and 0∶00, the rats were given helicid 50 mg/kg by gavage, respectively. Blood samples were collected from ophthalmic venous plexus. Then plasma concentration was measured. Pharmacokinetic behaviors of the original drug and its metabolites after administration at different time points were calculated and compared. RESULTS: This established HPLC-MS/MS method was successfully applied to simultaneous determination of helicid and its three metabolites in rat plasma after intragastric administration. Using AUC(0-t) as evaluation index of degree of absorption, the original drug, oxidation product, and reduction product in the 8∶00 administration group were all >0∶00 administration group and >14∶00 administration group; at the same time point compared with the metabolites, 8∶00 administration group, 14∶00 administration group, and 0∶00 administration group were: original drug>reduced metabolite>oxidized metabolite. Cmax original drug 0∶00 administration group>8∶00 administration group>14∶00 administration group, reduction and oxidation metabolites were 8∶00 administration group>14∶00 administration group>0∶00 administration group. Tmax original drug and reduced metabolite 8∶00 administration group>14∶00 administration group>0∶00 administration group, oxidation metabolite 8∶00 administration group>0∶00 administration group>14∶00 administration group. Clearance characterized by CLz/F, the original drug, reduction metabolite and oxidation metabolite were all 14∶00 administration group>0∶00 administration group>8∶00 administration group. CONCLUSION: The three specific time points selected in this study, absorption and metabolism process of helicid and its metabolites showed great differences. The absorption degree of administration at 8∶00 was greater than the other two time points (P<0.01), and the elimination of the original drug and metabolites from the body at 14∶00 was much faster than that at other time points (P<0.01).

Key words: helicid, chronopharmacokinetics, metabolite, absorption, metabolism