| Fibrauretin has antibacterial, antiviral, arrhythmias, enhancing immunity and so many kinds of physiological activity, but the bioavilability is low due to poor water-soluble and strong first pass effection. This assay studies on pharmacokinetic of fibrauretin crude drug in order to get the pharmacokinetic parameters,and the dosage forms and auxiliary material selection accord to it. Prescription process optimizes through orthogonal design.This assay makes fibrauretin pellets capsule quality standard from many aspects. This assay study on relative bioavilability basing on the fibrauretin pellets capsule as test dosage and fibrauretin as reference dosage. Study the following:1. Fibrauretin pharmacokinetic studies. Fibrauretin blood concentration determine by HPLC-MS/MS method, there is none of endogenous substances interference, high sensitivity,the lowest limit of qulification0.2ng/ml,good linear relationship from0.2ng/ml to125ng/ml,method recovery of1.3.43%,intra and inter precision less than11.5%,extraction recovery74.59%and82.13%for fibrauretin and inter standard, plasma sample can be stable in different storage conditions. The analysis method of the fibrauretin can meet the requirements of the pharmacokinetic studies. Rats were given low, medium and high doses of60mg/kg,120mg/kg,240mg/kg. Blood drug concentration is calculated by the the form building analysing method. Use of DAS2.0analyses data, records pharmacokinetic parameters, and analyzes the significance of the parameters. Giving low, medium and high different doses, fibrauretin are of all Cmax less than55ng/ml, AUCO-less than395ng/ml.,so the absorption of fibrauretin is poor. The AUCO-∞equaling dose are close therefore fibrauretin in the body are close to linear pharmacokinetic process.2. Fibrauretin pellets prescription technology study。Considering fibrauretin absorption is poor, joining twain-80, PEG-4000as absorption promoting agents。 according to the results of the experiment many times the, establishing four basic prescription, according to the same length pellets, appearance determine basic prescription. Through the single factor investigation found that microcrystalline fiber dosage, rounded rate, the dosage of wetting agents influence the quality of fibrauretin pellets.Orthogonal design determined the best prescription process for microcrystalline fiber dosage rate33%, rounded for32Hz, wetting agent for215mg. According to the best prescription, we produce three batch of samples, and preliminaryly evaluate the three samples, and three products comply with pharmacopoeial requirements about the capsule. 3. Fibrauretin pellets quality evaluation study. Through the chemical, ultraviolet and high performance liquid identify showed that materials content is without interferece of fibrauretin determination.Three group of samples to check for content difference, the results of three samples comply with pharmacopoeial requirements for content. Samples of fibrauretin pellets acid damage, alkalid damage test, degradation products don’t interfere with the determination of fibrauretin pellets; fibrauretin pellets sample their own controlled trials found that impurity content in fibrauretin pellets is less than3%. Establishing fibrauretin content determination of HPLC method, choosing345nm wavelength for absorption, choosing fibrauretin sample processing method is adding1%HCl methanol20ml, ultrasounding treatment20min, putting cold to room temperature, with1%HCl methanol dilution to scale, filtration, taking renewal filtrate1ml, the capacity to25ml, for a quick. Durability test, to determine the chromatographic conditions for:ZorBax Eclipse XDB-using C18column (4.6×250mm,5μ m); Mobile phase for: acetonitrile-0.4%phosphoric acid (25:75); Velocity1.0ml/min; The column temperature40℃; Determining wavelength345nm.Materials content is without interferece of fibrauretin determination;0.0110-0.1754mg/m range, linear relationship is good, precision RSD (%) is2.23%, repeatability RSD (%) is0.33, Fibrauretin samples can be stable at least24h, average recovery rate is100.10%:this method are in line with the fibrauretin content determination fibrauretin pellets requirements.4. Fibrauretin pellets relative bioavailability study. Fibrauretin blood concentration determine by HPLC-MS/MS method, there is none of endogenous substances interference, high sensitivity.the lowest limit of qulification0.2ng/ml,good linear relationship from0.2ng/ml to125ng/ml,method recovery of101.42%,intra and inter precision less than8%,extraction recovery73.33%and83.22%for fibrauretin and inter standard, plasma sample can be stable in different storage conditions. The analysis method of the fibrauretin can meet the requirements of the bioavailability studies. Fibrauretin pellets relative bioavailability is110.21%... |
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