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Study On The Pharmacokinetics Of Scutellarin And An Unknown Metablite In Animals

Posted on:2007-09-10Degree:MasterType:Thesis
Country:ChinaCandidate:C G DingFull Text:PDF
GTID:2144360212457766Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
The pharmacokinetics of scutellarin was investigated after intravenous injection in mouse, rat and rabbit. Scutellarin was quickly eliminated in the plasma. The mean value of t1/2β was 100.2,79.4 and 28.1min,respectively. An unknown compound was found in the plasma of mouse and rat post dose, which may be a new metabolite of scutellarin.The ratio of scutellarin binding to human plasma was determined by equilibrium dialysis. When the plasma concentration of scutellarin was 3.3-37.4μg/ml, the biding ratio was 90.59-93.87%.The ultraviolet spectrums of the unknown compound and scutellarin were determined under the same condition. The ultraviolet spectrums of two compounds are similar. The wavelengths of maxim absorbency for the unknown compound are 334, 271nm. The unknown compound was separated from the small intestme of mouse with solid phase extraction, and its structure was investigated with tandem mass technique. The molecular formula of the unknown compound is C27H26O18. It is the glucuronide-conjugated product of scutellarin. This metabolite (M) was reported firstly. We also confirmed the metabolite extracted from small intestine is the same as the unknown compound in the liver and plasma.A HPLC method for simultaneous determination of M and scutellarin was established, and had been applied to the pharmacokinetic study of mouse and rat. When the plasma concentration of scutellarin decreased, that of M increased sharply to the level of scutellarin, and then the two compounds were eliminated at the similar rate. M is not found in the plasma of rabbit post dose, which indicated species differences in metabolism.The metabolism pathway of scutellarin was discussed based on comparing the peak area ratio of scutellarein to scutellarin in raw material and the plasma of mouse post dose. Compared with the lost of glucuronide, glucuronide-conjugated is the main trend of scutellarin's metablism in mouse for intravenous injection.
Keywords/Search Tags:scutellarin, breviscapine, pharmacokinetics, metabolism, LC-MS/MS
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