ABSTRACT
OBJECTIVE:To study the metabolite and excretion of polydatin (Trans-resveratrol-3-O-glucoside,TRG) and its metabolites in Beagle dog feces,and provide experimental basis for the new drug development of TRG. METHODS:4 Beagle dogs were intragastrically administrated TRG 20％ polyethylene glycol 400 solution 50 mg/kg. LC/MS was used to identify the me-tabolites of TRG in dog feces after 12-24 h of administration,and HPLC was adopted to determine the cumulative excretion rate and excretion speed rate of the major metabolite resveratrol(TR)in feces samples after 0-12,12-24,24-36,36-48,48-72,72-96 h of administration. RESULTS:TR and two sulfate conjugates of TR were found in dog feces,and TR was a major metabolite, while TRG was undetermined. The excretion speed rate of TR in dog feces was the rapidest after 12-24 h of administration,reach-ing 9.65 mg/h. Its cumulative excretion rate was 39.3％,equivalent to 67.2％ of TRG. CONCLUSIONS:After TRG is intragastri-cally administrated to dogs,TRG was mainly excreted in the form of TR via dog feces.
ABSTRACT
OBJECTIVE: To establish a HPLC method for the determination of serum concentration of caffeic acid in rats and which was applied to the pharmacokinetic study of caffeic acid. METHODS: The concentrations of caffeic acid in rats were determined after intragastric (ig) administration or intravenous (iv) administration of 50 mg?kg-1 caffeic acid and the pharmacokinetic parameters of caffeic acid analyzed by Topfit 2.0. RESULTS: The main pharmacokinetic parameters of caffeic acid after ig administration of caffeic acid were as follows: Cmax: (0.56?0.12) ?g?mL-1; tmax: (0.18?0.04) h; t1/2: (0.67?0.12) h; ke: (1.05?0.20) h-1; AUC(0～t): (0.34?0.05) ?g?h?mL-1. The main pharmacokinetic parameters of caffeic acid via iv administration were as follows: t1/2: (0.45?0.05) h; ke: (1.55?0.18) h-1; AUC(0～t): (9.07?2.24) ?g?h?mL-1. CONCLUSION: Administered intragastrically, caffeic acid was characterized by rapid absorption, short elimination half life (t1/2) and low absolute bioavailability in rats.
ABSTRACT
OBJECTIVE:To determinate the metabolites of ranolazine in rats by LC-MSn.METHODS:Rats were given 80 mg?kg-1 ranolazine by i.g.During 0～24 h after intragastrical administration,the sample of urine was collected and extracted by solid phase column.Extracts were determined by LC-MSn.The mobile phase consisted of acetonitrile,10 mmol?L-1ammonium acetate and glacial acetic acid at a flow rate of 0.5 mL?min-1.Fragmentation ions of ranolazine and its metabolites were determined in positive electrospray ionization by using MS,MS2 and MS3 full scans.RESULTS:Twelve phaseⅠ metabolites (O-demethylation,O-dearylation,hydroxylation,N-dealkylation and amide hydrolysis) and nine phase Ⅱ metabolites(O-glucuronidation and sulfation) were found in the sample.CONCLUSION:Ranolazine is extensively metabolized in rats.