The majority of modern antidepressants (selective serotonin reuptake inhibitors and selective serotonin and norepinephrine reuptake inhibitors) have one or two centers of asymmetry in their structure; resulting in the formation of enantiomers which may exhibit different pharmacodynamic and pharmacokinetic properties. Recent developments in drug stereochemistry has led to understanding the role of chirality in modern therapy correlated with increased knowledge regarding the molecular structure of specific drug targets and towards the possible advantages of using pure enantiomers instead of racemic mixtures. The current review deals with chiral antidepressant drugs; presenting examples of stereoselectivity in the pharmacological actions of certain antidepressants and their metabolites and emphasizing the differences between pharmacological actions of the racemates and pure enantiomers.
Citalopram (CIT) is a frequently used modern antidepressant that inhibits selectively serotonin reuptake in the brain. It has a chiral center in its structure and is used in therapy as both racemic mixture and pure enantiomer as its pharmacological effect is almost entirely associated with S‐CIT. The aim of this study was the development of a simple and rapid capillary electrophoresis (CE) method for the separation and quantification of CIT enantiomers. To establish the optimum chiral selector, several native and derivatized, neutral, and ionized cyclodextrins (CDs) were examined at different pH levels. An experimental design strategy was adopted for method optimization; a fractional factorial design was applied for screening purposes to identify significant experimental factors followed by a face‐centered central composite design used for optimization purposes. Computational modeling was used to obtain information on the interaction energy and the geometry of the complexes to aid in the understanding of chiral separation mechanism. The best results were obtained when using a 25‐mM phosphate buffer at pH 7.0, 3‐mM CM‐β‐CD as chiral selector, 17.5°C temperature, 15‐kV voltage, and 50 mbar/s hydrodynamic injection. The separation time was fast, below 3 min, and the migration order was S‐CIT followed by R‐CIT. The analytical performance of the method was verified in terms of precision, linearity, accuracy, sensibility, and robustness, and the method was applied for the determination of CIT enantiomers from pharmaceutical preparations.
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