| 1ObjectiveThis topic is on the basis of the content of the National Natural Science Foundation (NO.30,701,097), the comparative study dehydroandrograpHolide and Chuanxinlian intestinal absorption characteristics and pHarmacokinetics of the similarities and differences. The investigated dehydroandrograp Holide different species of the plasma stability and to explore the factors that affect plasma stability. The establish ultrafiltration method for the determination of plasma protein binding rate in dehydroandrograpHolide investigated the dehydroandrograpHolide in different species of plasma protein binding rate. Intestinal sac the valgus France dehydroandrograpHolide intestinal absorption mechanism, and contrast study dehydration of andrograpHolide and AndrograpHis paniculata in the duodenum, jejunum, colon, cecum, the absorption characteristics. The establishment of a dedicated, rapid and sensitiveLC/MS/MS method,determination of the plasma dehydroandrograp Holide, and applied to study medicine dehydroandrograpHolide and AndrograpHis move clarify dehydroandrograpHolide with AndrograpHis paniculata in the pHarmacokinetics of differences.2Methods and Results2.1AndrograpHis refined matter contentTo establish an HPLC-UV chromatograpHic method for determination of andrograpHolide and dehydroandrograpHolide measured the content of the refined things in AndrograpHis paniculata AndrograpHolide and dehydroandrograpHolide late intestinal absorption and pHarmacokinetic study provide a reference. The use of chromatograpHic conditions:mobile pHase:A mixture of acetonitrile, B is the water gradient elution. A hand in hand time for30%(0-3min),30%to55%(3min-10min).55%(10min-16min),55%-30%16min20min); flow rate:1mL·min-1; column temperature: room temperature; detection wavelength:245nm. The drograpHolide dehydroandrograpHolide in0.2473u g·mnL-1-19.78g■mL"’,0.252u g■mL"1^20.16u g■mL"1a good linear relationship. AndrograpHis refined extract andrograpHolide content of16.8%, dehydroandrograpHolide content of4.7%o2.2dehydroandrograpHolide plasma protein bindingThe establishment of the BSA, rat plasma, ultrafiltration sample dehydroandrograpHolide Method for determination of human plasma. Ultrafiltration method for the determination of plasma of different species of the dehydroandrograpHolide BSA, rat plasma, human plasma protein binding rate. Using chromatograpHic conditions:mobile pHasei, methanol-water (70:30); flow rate:1mL■min"1; column temperature:room temperature; detection wavelength:254nm. Of dehydroandrograpHolide with BSA, normal human plasma, rat plasma protein binding rate (71.50■1.50)%(79.91■2.51)%(82.41■2.05)%, belonging to the combination of moderate-intensity, and DehydroandrograpHolide lactone with a combination of drug concentration-dependent plasma between different species of significantly different.2.3The dehydroandrograpHolide blood stabilityTo establish an HPLC-UV chromatograpHic method for determination of BSA in rat plasma, human plasma drug concentration dehydroandrograpHolide. DehydroandrograpHolide in PBS remained stable for at least4hours. DehydroandrograpHolide BSA, normal human plasma, rat plasma at room temperature (20■C), frozen (-20■C) conditions remain stable at least within12hours stored in ice (-4■C) conditions stored at least in the30d remained stable. DehydroandrograpHolide the BSA, normal human plasma, the stability of the plasma from rats no significant difference. Good stability to meet dehydroandrograpHolide study in rats in vivo drug action.2.4monomer dehydroandrograpHolide and AndrograpHis refined and intestinal absorption characteristics Intestinal sac eversion method research monomer dehydroandrograpHolide AndrograpHis refined extract of intestinal absorption characteristics. The monomer dehydroandrograpHolide and AndrograpHis refined extract dehydroandrograpHolide absorption are passive absorption in the duodenum, jejunum, ileum, colon, four heartbroken and no significant difference between each bowel. Four heartbroken study of the duodenum, jejunum, ileum, colon, refined extract of AndrograpHis paniculata dehydroandrograpHolide absorb strong monomer dehydroandrograpHolide, absorb faster, total absorption increases, but no significant difference (P>0.5).2.5monomer dehydroandrograpHolide AndrograpHis refined extract pHarmacokinetic studiesThe establishment of the determination of the method dehydroandrograpHolide in rat plasma by LC/MS/MS using the classical plasma concentration France, respectively, oral give dehydroandrograpHolide monomer and AndrograpHis refined extract capillary canthus blood, determination of plasma concentration change over time, the drug is drawn curve data, through winnonlin software processing, fitting the best way to model comparison monomer dehydration AndrograpHolide and Chuanxinlian, refined extract dehydroandrograpHolide pHarmacokinetics in the rat, the similarities and differences. By LC/MS/MS conditions were detected using electrospray ionization source in negative ion mode (ESI-), the spray voltage is3500V, heated capillary temperature of320C, sheath gas and auxiliary gas N2sheath gas pressure of30psi, auxiliary gas pressure of10psi, collision gas was argon; choice reaction (SRM) mode detection, the parent ion at m/z331ion atm/z309; a collision energy30ev, the two collision energy25ev.. The chromatograpHic conditions were as follows:mobile pHase:acetonitrile-water-formic acid=35-65-0.1%, flow rate of0.2mL·min-1, oven temperature:30°C, the sample chamber temperature:4°C.Monomer dehydration the same content of dehydroandrograpHolide in andrograpHolide administered group and the low dose group of AndrograpHis paniculata refined extract treatment group of high school, namely:the high dose group:30mg/kg,15mg·kg-1dose group, low dose group of7.5 mg· kg-1of the monomer AndrograpHis paniculata treatment group Tmax high, medium and low doses were0.40,0.67,0.45h, the Cmax for55.42,44.56,7.27ng· mL-1, respectively high, medium and low doses of AndrograpHis paniculata refined extract treatment group Tmax0.48,0.31,1.06h, the Cmax441.17,135.38,115.71ng· ml-1, no significant difference between the monomer administered group and the refined extract administration group Tmax, indicating that the monomer andrograpHolide and AndrograpHis refined extract the DehydroandrograpHolide ester was no significant difference in the absorption rate. The single dose group of cmax are less than the refined extract treatment group, indicating that the refined extract of DehydroandrograpHolide dehydroandrograpHolide called monomer administered more easily absorbed. CL were of high, medium and low doses of the single dose group25094.17,8630.30,19464.80mL· hr-1, high, medium and low doses of refined extract treatment group CL were2046.99,28620.08,7186.77mL· hr-1AndrograpHis refined extract treatment group CL were lower than the single dose group, indicating that the single dose group to pay the the AndrograpHis refined extract treatment group in order to eliminate, in the short residence time in vivo. Vd, respectively, of high, medium and low doses of the single dose group, for232974.18,37688.52,57419.00mL, refined extract high, medium and low-dose administration group Vd, respectively, for26497.19,15705.12,13117.33mL, volume of distribution of refined extract treatment group were less than a single body dose group, indicating that the monomer dosing compared with AndrograpHis refined extract treatment group is difficult to absorb.4ConelusionThe dehydroandrograpHolide plasma with moderate combined with differences in plasma between different species. The dehydroandrograpHolide with good stability in the BSA, normal human plasma, rat plasma. DehydroandrograpHolide the BSA, normal human plasma, the stability of the plasma from rats no significant difference. Monomer dehydration the AndrograpHolide Chuanxinlian refined extract is a passive absorption in the duodenum, ileum, colon, jejunum, no special absorption window refined extract of AndrograpHis paniculata accumulation of intestinal absorption is better than the monomer dehydroandrograpHolide but no significant differences. In rats, AndrograpHis refined administration than the monomer administered dehydroandrograpHolide more easily absorbed, eliminating slow down, retention time in vivo bioavailability. Monomer components pHarmacokinetic and compound pHarmacokinetics may have differences, need to be carefully treated. |
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