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The goal of this work is to investigate the direct chromatographic separation of the enantiomers of fluoxetine and its active metabolite norfluoxetine. The liquid chromatographic retention behavior of these enantiomers on a P-cyclodextrin bonded-phase column was investigated with respect to mobile phase composition, pH, ionic strength, and solvent selectivity. Relationships were established between these factors and the three most important chromatographic parameters: retention time, resolution, and selectivity. Most of the evidence suggests that the unique selectivity of this column isdue to inclusion complex formation, which provides the physical basis for enantiomeric resolution. After these studies a set of optimum chromatographic conditions was chosen for the simultaneous separation/ determination of a mixture of the four enantiomers using fluorescence detector. Since FL is marketed as a racemic mixture, the pharmacology, metabolism, and pharmacokinetics of the enantiomers of FL and its metabolites have important clinical implications. The enantiomers of FL exhibit the biochemistry and pharmacology in vitro and in vivo of selective 5-HT uptake inhibitors with about equal potencies.However, many differences have been reported in the literature with regard to their relative pharmacological potencies. (+)-(S)-FL appears to be slightly more potent than (-)-(R)-FL in blocking 5-HT uptake in vivo or preventingp-chloroamphetamine induced depletion of brain 5-HT.4 (+)-(3-FL was also seen more potent when the two enantiomers were compared for their abilities to lower food intake in meal-fed rats and in 2-deoxyglucose-induced hyperphagic rats. serotonin uptake activity of (+)-(S)-NR was 16-fold greater in vitro and 20-fold greater in vivo than that of (-)-R-NR.7*8 Therefore, the difference in the duration of action between the isomers of FL can be partially explained on the basis of conversion of (-)-(R)-FL to the relatively inactive (-)-(R)-NR.A limited number of analytical methods have been reported for the assay of FL and NR in biological Only one of these methods7 was capable of successfully separating and quantitating the enantiomers of FL and NR using an indirect chromatographic procedure (chiral derivatization). The present work describes a simple, sensitive, and direct chromatographic method for the determination of the enantiomers of FL and NR using fluorescence detection.Optical resolution by direct chromatography is possible through reversible diastereomeric association between a chiral selector introduced into a column and the solute enantiomers. For the application of cyclodextrins (CDs) in this stereoselective process, two different approaches have been recently designed the use of chemically bonded cyclodextrins (CDs) silica stationary phased3 and the application of CDs as mobile phase additives in RP-HPLC. l4 In this paper the use of a P-cyclodextrin bonded stationary phase has been used to investigate the resolution of the enantiomers of fluoxetine and

A p-cyclodextrin-bonded phase has been used to investigate the separation of the enantiomers of atenolol, oxprenolol, celiprolol, tertatolol, terbutaline, fluoxetine, norfluoxetine, and zopiclone, focusing on the importance of solvent selectivity. With cyclodextrin (CD)-bonded phases, chiral discrimination occurs because the two enantiomers of a racemate form inclusion complexes of different strengths within the CD cavity. The organic modifier molecules tend to compete with solutes for a definite number of adsorption sites on the stationary phase. Moreover, the ternary complex formation may play an important role in chral recognition. In h s study, it was of interest to estimate the mfluence of mobile phase modifiers with respect to solvent type (i. e., ACN, MeOH, EtOH, THF, i-PrOH, PrOH and t-BuOH), size and shape, and concentration. Solvent selectivity has been investigated by using different organic modifiers in mobile phases with the same polarity, and relationships were established between the logarithm of solvent partition coefficient (log P,) and the three most important chromatographic parameters: retention time (t), resolution (R), and enantioselectivity (a). Thus, it seems that the hydrophobicity of the organic modifier becomes one of the dominant factors affecting the inclusion process phenomena. Further, the apparent partition coefficients of the compounds under study have been determined and a comparison has been attempted regarding the degree of their enantiomeric resolution. KEY WORDS: enantiomeric separation, p-blockers, zopiclone, fluoxetine, norfluoxetine, promethazine, apparent partition coefficient In RPLC, retention is described mainly as a function of its solvophobic interaction. It is also known that retention is a sensitive function of the quantitative (strength) and qualitative (selectivity) composition of the mobile phase.Theoretically, solvent selectivity, primarily refers to the ability of a solvent to exhibit specific solute interactions which another solvent of approximately similar strength or polarity does not have. Polarity describes the gross solvent strength. Selectivity describes the fine structure of strength, the profile of polarity subparameters. 2*3In HPLC, in order to describe the strength and the selectivity of the different solvents, various workers have proposed different parameters such as P' (Snyder's polarity index), S (solvent strength parameter), 8-,. (solubility parameter), and P, (partition coefficient).Our initial motivation in undertaking this work was to investigate the role of solvent selectivity on the chromatographic enantiomeric separation of a series of racemic mixtures using a p-cyclodextrin-bonded phase, i. e., atenolol (AT), oxprenolol (OX), celiprolol (CE), tertatolol (TE), terbutaline (TB), fluoxetine (FL), and norfluoxetine (NRh4 zopiclone (ZP), as well as promethazine (PR) and its positional isomer5 (Fig. 1).Cyclodextrins (CDs) are cyclic oligosaccharides composed of six or more glycopyranose moieties bonded together via a-(l,U-linkages. Ge...

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Computers in chemistryComputers in chemistry V 0380 A New Approach to Predict the Biological Activity of Molecules Based on Similarity of Their Interaction Fields and the logP and logD Values: Application to Auxins. -(BERTOSA, B.; KOJIC-PRODIC, B.; WADE, R. C.; RAMEK, M.; PIPERAKI, S.; TSANTILI-KAKOULIDOU, A.; TOMIC*, S.; J. Chem. Inf. Comput. Sci. 43 (2003) 5, 1532-1541; Ruder Boskovic Inst., HR-10000 Zagreb, Croatia; Eng.) -Lindner 50-241