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Studies On Preclinical Pharmacokinetics Of Dencichine And Bioequivalence Of Rabeprazole

Posted on:2007-06-29Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y ZhangFull Text:PDF
GTID:1104360185451610Subject:Drug Analysis
Abstract/Summary:PDF Full Text Request
Dencichine (β-N-oxalyl-L-α,β-diaminopropionic acid), a nonprotein amino acid, isolated from Panax notoginseng, has been shown beneficial effects on hemostasis. Panax notoginseng (Burk.) F. H. Chen (commonly known as Tianqi or Sanqi) is a highly valued and important Chinese medicinal herb produced mainly in Yunnan Province, China. For years, the raw form of Panax notoginseng has been a valuable herb widely used in Chinese medicine for its hemostatic and cardiovascular properties to arrest various internal or external haemorrhage, eliminate blood stasis, improve blood circulation, disperse bruises, reduce swelling and pain. Studies have reported dencichine as the component responsible for the medicinal herb's main haemostatic and platelet-increasing properties in vivo.In present paper, pharmacokinetics of dencichine in rats and dogs were investigated. Precolumn derivatization was used to improve the sensitivity in the liquid chromatographic-tandem mass spectrometric method for determining of dencichine in plasma. The metabolism, excretion and tissue distribution of dencichine in rats were studied to support the pharmacology and toxicology study of dencichine. The plasma protein binding and enzyme inhibition studies were also performed in this paper.Rabeprazole is a new proton pump inhibitor. A sensitive, rapid and specific liquid chromatographic-tandem mass spectrometric (LC/MS/MS) method for the determination of rabeprazole in human plasma was developed. In the experiment, the stability of rabeprazole in solutions had been investigated. The method is proved to be suitable for clinical investigation of rabeprazole pharmacokinetics and bioavailability. 1. Studies on pharmacokinetics of dencichine in rats and dogsA sensitive method was developed for the determination of dencichine in the plasma using a derivatization step to enhance signal intensity. The method consisted of a protein precipitation followed by derivatization with 10 M hydrochloric acid-methanol (10: 90, v/v) and analysis by liquid chromatography coupled with tandem mass spectrometry via atmospheric pressure chemical ionization (APCI) source.
Keywords/Search Tags:dencichine, pharmacokinetics, liquid chromatography-tandem mass spectrometry, precolumn derivatization, metabolism, rabeprazole, bioequivalence
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