[Pharmacokinetics of 8-O-acetylharpagide and harpagide after oral administration of Ajuga decumbens extract in beagle dog].
8-O-acetylharpagide and harpagide are two kinds of effective component of Ajuga decumbens extract. A sensitive LC-MS/MS method has been established for pharmacokinetics of 8-O-acetylharpagide and harpagide in beagle dog after oral administration of from A. decumbens extract. Female beagle dogs received orally 12.9, 25.7 mg x kg(-1) p. o. Concentrations of 8-O-acetylharpagide and harpagide in plasma were determined by LC-MS/MS method at different time points and all pharmacokinetic parameters were estimated by non-compartment analysis. The mobile phase consisted of 0.1% formic acid in water (A) and acetonitrile (B), which was run at a flow rate of 0.3 mL x min(-1). Chromatographic separation was achieved on an Agilent ZORBAX XDB-C18 column (2.1 mm x 50 mm, 3.5 microm) using a gradient elution of 5% B at 0-2 min, 95% B at 2. 1-5 min and 5% B at 5. 1-10 min. All analytes, including the IS, were monitored under positive ionization conditions and quantified in MRM mode with transitions of m/z 429.2-369.2 for 8-O-acetylharpagide, m/z 387.2-207.2 for harpagide, and m/z 149.2-103.1 for IS. High purity nitrogen was employed as both the nebulizing and drying gas. Other parameters of the mass spectrometer were optimized as follows: drying gas flow 10.0 L x min(-1); drying gas temperature 300 degrees C; capillary voltage 4 000 V. Results showed that 8-O-acetylharpagide and harpagide showed a dose-dependence profile. T(max) of 8-O-acetylharpagide is 1.7 h, and T(max) of harpagide is 1.57 h, which was higher than T(max) of 8-O-acetylharpagide and harpagide after oral administration of from A. decumbens extract in rats. The different pharmacokinetic parameters may be due to the species differences of rat and beagle dog.
Konruns Pharmaceutical Co., Ltd, Postdoctoral Workstation of Zhongguancun Haidian Science Park, Beijing 100085, China. wen-binyu@163.com
Bin-Yu
BY
Wen
Jian-Rong
JR
Li
D000284:Administration, Oral; D031328:Ajuga; D000818:Animals; D004285:Dogs; D005260:Female; D057889:Iridoid Glycosides / Q000493:pharmacokinetics*; D010936:Plant Extracts / Q000378:metabolism*; D011714:Pyrans / Q000493:pharmacokinetics*; D051381:Rats; D013045:Species Specificity
D057889:Iridoid Glycosides; D010936:Plant Extracts; D011714:Pyrans; C077626:8-O-acetylharpagide; C033250:harpagide