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Effects Of Styrene - Butadiene - Phthalocyanine In - Situ Metabolic Method In Target Tissues Of Rats And Salvia Miltiorrhiza Metabolism Of Traditional Chinese Medicine

Posted on:2005-09-07Degree:DoctorType:Dissertation
Country:ChinaCandidate:J P QiaoFull Text:PDF
GTID:1114360185973556Subject:Drug analysis
Abstract/Summary:PDF Full Text Request
6-Aminobutylphthalide (ABP) is a new drug candidate which has promising protective action against cerebral ischemia. The time course for the appearance and disappearance of ABP after oral administration to rats was provided, and the structure of the main metabolite was identified. For comparative purpose, tissue samples were analyzed using HPLC-UV, LC-MS/MS and GC-MS, the structure of the metabolite was validated.Additionally, the effects of the aqueous extract of Salvia miltiorrhiza Bge on liver microsomal cytochrome P450 enzyme activity and on the pharmacokinetics of diazepam in rats were studied. The pharmacokinetics and biotransformation of tanshinone IIA in rats were also investigated.1. Determination of ABP and its main metabolite in the brains of awake freely-moving rats by LC-MS/MSThe purpose of this study was to determine the time course of ABP concentrations and its main metabolite using the in vivo microdialysis sampling in the target organ. The concentrations of ABP in striatum of rats were determined using LC-MS/MS method on an API3000 triple-quadrupole mass spectrometer, the MRM mode was performed by monitoring the transition between m/z 206 and m/z 150, the limit of detection was 2.0 ng ml-1 for ABP. The concentration-time profile of ABP in the target organ was provided.The main metabolite of ABP in dialysates of brain striatum was identified by LC-MS/MS method on an LCQ ion trap mass spectrometer. The results showed the main metabolite of ABP was N-acetylated product (M1). The relative quantity change of ABP and Ml were compared. This study demonstrated that the microdialysis technique in combination with LC-MS/MS has a number of analytical advantages, such as excellent selectivity, specificity and without time-consuming sample clean-up procedures.
Keywords/Search Tags:phthalocyanine
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