Studies On The Enantiomeric Separation Of Chiral Drugs And The Pharmacokinetics

The enantiomeric separation of Chiral Drugs plays an important role at present scientific fields. Two enantiomers of many drugs possess different pharmacokinetic and pharmacodynamics and pharmacological action. Accordingly, to develop a enantiomeric separation method of fast, accurate and high-performance has important significance for developing new drugs, monitoring enantiomeric stereoselectivity and researchering enantiomeric physiological activity. In this paper, high performance liquid chromatography method using chiral stationary phases (HPLC-CSP) has been developed for separation of five drugs: sibutramine, nitrendipine, trimebutine maleate, ondansetronand and pantoprazole sodium. Chiral HPLC determination of dextro enantiomer for levo-pantoprazole sodium and the stereoselective pharmacokinetics of pantoprazole sodium in human plasma have been studied.1. Studies on the separation methods of enantiomers for sibutramine and nitrendipineClinically, sibutramine and nitrendipine are all administered as racemates. High performance liquid chromatographic(HPLC) methods have been used for the direct resolution of the two chiral drugs with aα₁-AGP Chiral stationary phase. The influences of organic solvent, the concentration and pH value of the buffer, the flow rate and the column temperature on the enantiomeric separation were investigated. And the enantiomeric separation was optimized. Sibutramine and nitrendipine enantiomers can be separated completely onα₁-AGP chiral stationary phase. The method is simple, rapid and reproducible.2. Studies on the separation methods of enantiomers for trimebutine maleate, ondansetronand and pantoprazole sodiumHPLC methods have been developed for the enantiomeric separation of trimebutine maleate, ondansetron and pantoprazole sodium on a Chiralpak AD-H Chiral column under normal phase mode. The influences of organic solvent, the concentration of glacial acetic acid and triethyamine, column temperature and flow rate on the enantiomeric separation were investigated and the enantiomeric separation were optimized. The three drugs enantiomers can completely on Chiralpak AD-H stationary phase. The proposed method was established to be simple, rapid and reproducible.3. Studies on chiral HPLC determination of dextro enantiomer of levo-pantoprazole sodiumLevo-pantoprazole sodium has better therapeutic effect than pantoprazole sodium and there is no preparation going on sale. For levo-pantoprazole sodium, dextro enantiomer needs quality control as impurity. A proposed HPLC method using Chiralpak AD-H column was used for chiral separation and determination of dextro enantiomer of levo-pantoprazole sodium. The study provides a sensitive and reproducible method for the quality evaluation and control of dextro enantiomer in levo-pantoprazole sodium material and formulation.4. Studies on the stereoselective pharmacokineties of pantoprazole sodium in haman An achiral-chiral coupled method to determine the enantiomers of pantoprazole sodium in human plasma was established. Stereoselective pharmacokinetics was studied of pantoprazole sodium enantiomer after a single oral dose of sodium enteric coated tablet (pantoprazole sodium 40 mg) to human. The result showed, the plasma levels for levo-pantoprazole sodium were always higher than its antipode in six human. The mean AUC_0-t and C_max values for levo-pantoprazole sodium were 2.0 and 1.6 times of those of dextro enantiomer, respectively. Indicating that the pharmacokinetics of pantoprazole sodium in human was stereoselective.