Studies On The Chiral Separation Of Several Drugs And The Pharmacokinetics Of Venlafaxine

Chirality is a fundamental phenomenon that plays an important role in biological processes.A wide range of biological and physical functions are generated through molecular recognition because endogenous substances within biological systems interact with different enantiomers in decisively different ways. As a result of such chiral recognition,drug enantiomers may differ in their pharmacokinetic characteristics and pharmacological effect. The availability of chiral analytical separation methods are important in studying and understanding the pharmacokinetic processes ,the pharmacological and/or toxicological effects and quality control of many drugs.In this paper, HPLC methods using chiral stationary phases(CSP) have been developed for separation of four drugs : venlafaxine , ibuprofen, trimebutine and fudosteine.The enantioselective pharmacokinetics of venlafaxine in rat plasma have been studied.1.Studies on the separation methods of enantiomers for venlafaxine , ibuprofen and trimebutineClinically,venlafaxine , ibuprofen and trimebutine are all administered as racemates. Influences of the pH value of the mobile phase,the organic modifiers,the buffer concentration,the flow rate and the column temperature on the enantiomeric separation of the three drugs by HPLC using α₁-acid glycoprotein(α₁-AGP) CSP were investigated and the enantiomeric separation were optimized .Venlafaxine , ibuprofen and trimebutine enantiomers can be baseline separated on the ai-AGP column. 2.Studies on chiral HPLC determination of dextro enantiomer of FudosteineLevo-fudosteine is a mucoactive agent but its dextro enantiomer has no activity,so dextro-fudosteine needs quality control as impurity.Fudosteine enantiomers cannot be separated on an ai-AGP CSP because its chemical stracture.A HPLC method using chirobiotic T CSP has been developed for chiral separation and determination of dextro enantiomer of fudosteine.The study provides a simple and reproducible method for the quality evaluation and control of dextro-fudosteine in material and formulation.