Résumé
The present study was designed to determine the effects of puerarin pre-treatment on the pharmacokinetics of the oral anticoagulant agent warfarin and the antiplatelet agent clopidogrel in rats. In the treatment group, rats was gavaged with warfarin or clopidogrel after repeated treatment with puerarin at intraperitoneal doses of 20, 60, or 200 mg·kg(-1) for 7 days, while rats in the control group were administrated only with the same dose warfarin or clopidogrel. Plasma samples were obtained at the prescribed times and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The results showed that rats treated with puerarin at all the test doses of 20, 60 and 200 mg·kg(-1) were found to affect the pharmacokinetics of warfarin, but not clopidogrel, suggesting a potential herb-drug interaction between puerarin and warfarin.
Sujets)
Animaux , Mâle , Rats , Anticoagulants , Pharmacocinétique , Chromatographie en phase liquide , Clopidogrel , Calendrier d'administration des médicaments , Interactions médicaments-plantes , Injections péritoneales , Isoflavones , Pharmacologie , Antiagrégants plaquettaires , Pharmacocinétique , Rat Wistar , Spectrométrie de masse en tandem , Ticlopidine , Pharmacocinétique , Vasodilatateurs , Pharmacologie , Warfarine , PharmacocinétiqueRésumé
AIM@#To establish a sensitive and rapid liquid chromatographic-tandem mass spectrometry (LC-MS/MS) method for the quantitative analysis of dehydrated puerarin in rat plasma, and its application for pharmacokinetic studies.@*METHODS@#A plasma sample was pretreated by one-step protein precipitation by the addition of five volumes of methanol. The chromatographic separation was achieved on a Zorbax SB-C18 column (4.6 mm × 150 mm I.D. 5.0 μm, Agilent, USA) at 40 °C at a flow rate of 0.6 mL·min(-1) by an isocratic elution consisting of 10 mmol·L(-1) ammonium acetate in methanol and water containing 0.1% formic acid in a ratio of 20 : 80 (V/V). Detection was performed on a triple quadrupole mass spectrometer in multiple-reaction monitoring (MRM) mode. An atmospheric pressure chemical ionization (APCI) interface in positive ionization mode was used by monitoring the transitions from m/z 399.1→281.0 (dehydrated puerarin) and m/z 271.0→215.0 (internal standard, IS).@*RESULTS@#Calibration curves were linear in the concentration range from 1.50 to 5400 ng·mL(-1), and the lower limit of quantification (LLOQ) was 1.50 ng·mL(-1) in rat plasma. The accuracy and precision values, which were calculated from three different sets of quality control samples analyzed in sextuplicate on three different days, ranged from 95.73% to 103.18%, and from 4.33% to 7.86%, respectively.@*CONCLUSION@#The method was successfully applied to assess the pharmacokinetics of dehydrated puerarin after oral administration in rats.
Sujets)
Animaux , Femelle , Mâle , Rats , Chromatographie en phase liquide à haute performance , Méthodes , Stabilité de médicament , Médicaments issus de plantes chinoises , Métabolisme , Pharmacocinétique , Isoflavones , Sang , Métabolisme , Pharmacocinétique , Pueraria , Chimie , Rat Wistar , Spectrométrie de masse en tandem , MéthodesRésumé
The purpose of this study was to investigate the preparation and characteristics of curcumin phospholipid complex, including the effects of reaction time, reaction solvent, reaction concentration and reaction temperature. Preparation technology resulted in that 0.5 g curcumin and 10 g soy phospholipid dissolved in 100 mL anhydrous alcohol, were stirred 1 h in 50 degrees C waterbath, then steamed alcohol in decompression, collected solid residue and vacuum dried for 12 h. The physicochemical properties for the new complex including IR spectrometer, mass spectrograph and HNMR equipment were detected. As a result, the formation of the complex is based on the reaction between phospholipid polar group rounding phosphorus atom and curcumin. This result gave the evidence for the formation mechanism of phospholipid complex.