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Application Of Liquid Chromatography -Ion Trap Mass Spectrometry In Metabolic Studies Of Agmatine, Flavonoid Glucoside CTN-986 And AGEs Cross-link Breaking Agents

Posted on:2006-07-17Degree:MasterType:Thesis
Country:ChinaCandidate:H L WangFull Text:PDF
GTID:2144360155957588Subject:Drug Analysis
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Liquid chromatography - ion trap mass spectrometry (LC/ITMS) is an analytical technique that has the merits to obtain more specific structural data by using MSn experiments. LC/ITMS is widely used in vivo and in vitro metabolic studies, including pharmacokinetic research ADME screening of potential drug candidates, and it was also crucial for drug research and development.Agmatine can enhance opioid analgesia and prevent in vivo tolerance, decrease hyperalgesia accompanying inflammation, neuropathy and spinal cord injury. Agmatine metabolites in mammals including putrescine, spermidine, γ-guanidinobutyrate et al but acetyl agmatine has never be reported. By using solid-phase extraction to remove salts, coupled with stable isotope labeling, we successfully identified agmatine and its metabolite acetyl agmatine in rat urine. The structure of agmatine and acetyl agmatine were both characterized by MS2 and MS3 spectra. In recent years, flavonoids have attracted strong attention for their potential antioxidant, anti-inflammatory, antiproliferative and anticarcinogenic properties. But there is still debate on whether flavonoid glucosides can cross the intestinal barrier and blood-brain barrier as an intact molecule into circulating system and brain. We administrated mice with flavonoid glucosides CTN-986, plasma and brain homogenization were analyzed by liquid chromatography with UV detector and MS detector. Both methods showed evidence that CTN-986 at an intact form in mice blood and brain.The method of screen AGEs cross-link breaking agents by liver microsome and caco-2 cell with LC/ITMS is simple, practically and relatively high throughput. 67 tested compounds results showed that: (1) The core structure of AGEs cross-link breaking agents is stable when being incubated in microsome liquid. The relict-time curves show 4 types for different...
Keywords/Search Tags:liquid chromatography - ion trap mass spectrometry, drug metabolism, agmatine, CTN-986, AGEs cross-link breaking agent
PDF Full Text Request
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