| Cough and asthma anointed in clinical often used in the treatment of simply typechronic bronchitis, Breathing type chronic bronchitis and asthma (except Cardiac) and so on,for external use only. As a traditional Chinese medicine compound preparations, itcomposed by white mustard, kanziol, rhizoma corydalis, asarum, datura flower, appropriatematrix, etc. Since the complex chemical composition of traditional Chinese medicinecompound preparations, big mutual interference between components, indeterminateeffective drug substance, and after the drug into the body, drug ingredients is absorbed,metabolized, possible biological transformed, not by the original form existence, meantimeprocess was complex and subtlety. So the pharmacokinetic study was different from thechemical drug pharmacokinetics research. In recent years, for the drug were topicalexternal or target parts was the skin, those drugs, more and more attention to the drugpharmacokinetics rule in skin. Generally, choice one or several effective componentswhich the pharmacology clear and the structure were known from the traditional Chinesemedicine compound preparations as observation standards, through the chemical analysismethod to test the animals after be given the drug, several time points the observationstandard concentration in serum, urine or other tissue fluid. Applicate the pharmacokineticcalculation formula to measurement the drug concentrations-time data processing andpharmacokinetic parameters. In this paper, we choose the main ingredient-scopolaminefrom datura flower as the research object, to clarify the pharmacokinetics characteristics ofcough and asthma anointed after be percutaneous administrated.Objective:Using LC-MS/MS analysis method combines the microdialysis sampling technologysimultaneously determine the scopolamine free drug concentration in rat skin and bloodduring the specified time, observe the pharmacokinetics characteristics of the drugscopolamine in rat skin and blood.Methods:SPF male SD rats,18hours prior the experiment, take off abdomen and neck hair.Then implant the microdialysis probes into the naked belly skin and right jugular vein,respectively. After giving the scopolamine gel on bare belly skin, use the microdialysistechnical combine the LC-MS/MS analysis method to determine the scopolamineconcentration changes in tat blood and dermal simultaneously, the drug concentration dataprocessing with BAPP2.0software. Results:1、Optimize the perfusate flow rate and perfusion from the stability and relativerecovery, at last,we choice the PBS(pH7.4) be the best derfusion, and the perfusate flowrate was2uL/min. The in vitro recovery of scopolamine detected by the concentrationdifference method (increment method and decrement method, in vivo recovery detected bydecrement method. The in vitro recovery detected by increment method was accordancewith the decrement method, and this phenomenon both fitted for the linear probes andconcentric probes. The recovery decreased when the flow rate increased. Scopolaminerecovery was independent of scopolamine concentration in the external medium. The invivo recovery both for linear probes and concentric probe were (31.55±1.32)%and(19.06±2.00)%, respectively. The in vivo recovery of scopolamine was steady in6hoursboth for linear probes and concentric probes. So we can conclude that the microdialysistechnique can be employed to determine the pharmacokinetics of cough and asthmaanointed in rat dermis.2、After cough and asthma anointed be administered percutaneously, the scopolaminein skin microdialysates can be detected. But as caduet, the content of scopolamine wassmall, so during the experiment we can found the concentration of scopolamine inmicrodialysates always was small. The results can not express the change process of coughand asthma anointed in skin really. As results in this research we choose one monomer’scopolamine’ extracted from datura flower as an representative drug to explain thepharmaceutics process of cough and asthma anointed.3、After administrating scopolamine gel on SD rats local skin, collect microdialysissamples at different time points. Use the HPLC-MS/MS analysis method established aboveto determine the scopolamine concentrations in rat dermis and plasma microdialysates.Based on the drug concentration-time profile, calculate the pharmaceutics parameters bynoncompartment models. The result shows that the scopolamine Tmax in dermis andplasma were120min and125min respectively, Cmax were (939.35±167.75) ng/mL and(49.61±15.81) ng/mL respectively after employing scopolamine gel on rat’s localskin. Then the concentration both in dermis and plasma decreased slowly to a steadyconcentration, and maintain at this concentration until8h. Based on the store function ofskin, the mean MRT in dermis (291.331±9.128) was higher than the MRT in plasma(227.726±16.337).Conclusions: Microdialysis sampling technique has good time and space distinguishability. Whencombined it with the HPLC-MS/MS it can reflect the analyte pharmacokineticscharacteristic in dermis and plasma accurately and objectively, and it is a good tool todetermine the dermal pharmacokinetics. |
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