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.

Fluoxetine is an antidepressant, a selective serotonin reuptake inhibitor (SSRI) used primarily in the treatment of major depression, panic disorder and obsessive compulsive disorder. Chiral separation of racemic fluoxetine is necessary due to its enantioselective metabolism. In order to develop a suitable method for chiral separation of fluoxetine, cyclodextrin (CD) modified capillary electrophoresis (CE) was employed. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector. As a result of this process, heptakis(2,3,6-tri-O-methyl)-β-CD (TRIMEB) was selected for enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors are varied at the same time to optimize the separation method. The optimized method (50 mM phosphate buffer, pH = 5.0, 10 mM TRIMEB, 15 °C, + 20 kV, 50 mbar/1 s, detection at 230 nm) was successful for baseline separation of fluoxetine enantiomers within 5 min. Our method was validated according to ICH guidelines and proved to be sensitive, linear, accurate and precise for the chiral separation of fluoxetine.

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.

Chiral separation cetirizine, a second generation H1 antagonist was studied by cyclodextrine (CD) mediated capillary electrophoresis. The influence on the separation of several parameters including pH and concentration of the background electrolyte (BGE), CD type and concentration, applied voltage and temperature were studied and the electrophoretic and analytic parameters were optimized. The best conditions for the chiral separation were obtained using 25mM disodium hydrogenophosphate -25mM sodium didydrogeno-phosphate (1:1) as BGE, 5mM sulfobuthyl ether-β-CD as chiral selector, a voltage of + 20kV, temperature of 20°C, injection pressure/time of 50mbar/ 1sec, UV detection at 230nm. The analytical performance of the method was evaluated. The proposed method was successfully applied to the enantioselective assay of cetirizine in pharmaceutical formulations. CE proved to be a rapid, specific, reliable and cost-effective method for the chiral separation of cetirizine enantiomers and can be useful for laboratories performing routine analysis.