جداسازی باکلوفن انانتیومرها با استفاده از فاز ثابت سیلیس وانکومایسین
Abstract
1- Introduction
2- Experimental
3- Results and discussion
4- Conclusions
References
Abstract
The chiral separation of baclofen (Bac) was obtained by nano-liquid chromatography tandem mass spectrometry (nano-LC–MS/MS) using a 100 μm I.D. fused silica capillary column packed with silica particles chemically modified with vancomycin. Various experimental parameters, such as composition (buffer concentration, water content, organic modifier) and pH of the mobile phase and sample solvent were investigated for method optimization. In order to increase the sensitivity an on-column focusing procedure was applied. Acceptable separation of Bac enantiomers was obtained in less than 11 min eluting in isocratic mode, with 90:10 MeOH/water (v/v) containing 10 mM ammonium acetate at pH 4.5. These optimized experimental conditions were applied to the analysis of human plasma samples spiked with racemic mixture of Bac. The use of a Buckypaper disc as sorbent membrane allows one to recover both enantiomers with yields ≥ 65%. The method was fully validated, following the identification criteria of the European Commission Decision 2002/657/EC.
Introduction
Still today, chirality is a key topic of research because of the overriding importance of enantiomers in various areas such as environmental, food, pharmaceutical, and above all human health science. In this regard, it is worth mentioning that more than a half of the produced and prescribed drugs have one or more chiral centres [1] and, as a result, they exhibit one or more couples of enantiomers. It is well-known that drug/receptor interaction is greatly stereoselective. Consequently, only one of the two enantiomers can give the wanted pharmacological activity, whereas the other one may display inactivity, lower potency, toxicity, and even undesirable side effects. Moreover, in the pharmaceutical industry, the importance of single enantiomer preparation on drug pharmacodynamics or pharmacokinetics is still not completely understood, butin many countries, the regulatory agencies, engaged in the registration of new drugs,focus their efforts inlegislating for the registrationofthe single enantiomers. In this regards, pharmaceutical industries are asked to provide complete information about the stereochemistry and stereoselectivity of all chiral products as well as the stereoselective analytical techniques for their determination. In this context, US Food and Drug Administration and other health regulatory agencies have issued definite guidelines for both the marketing of chiral drugs and their enantiomeric separation [2].