EnantioselectiveLCanalysis and determination of selective serotonin reuptake inhibitors

Abstract

LC separation of biologically and pharmaceutically important enantiomers (from racemic or non‐racemic mixtures) remains a subject of importance. The present review article deals with the liquid chromatographic enantioseparation of chiral selective serotonin reuptake inhibitors (SSRIs), namely citalopram, paroxetine, sertraline and fluoxetine. It is now known that the enantiomers of numerous psychotropic drugs exhibit distinct pharmacodynamics, pharmacokinetic patterns and receptor binding properties, and psychiatric patients are frequently taking more than one medication. Therefore, monitoring of the levels of these analytes in biological fluids is important to determine the levels of enantiomer concentrations; the present paper may be helpful in understanding the present state of available methods (along with a critical discussion of applicability of the methods) and in developing the new ones for this purpose. Different approaches using LC discussed herein may be applied for determining the enantiomeric composition (and enantiomeric purity) of SSRIs and numerous other racemic drugs, of current/future pharmaceutical importance and utility, using simple separation methods, instrumentation, inexpensive reagents and potentially significant analytical approaches. The contents cover the essential data to understand the various separation techniques and associated issues, if any, with documented examples.

Assessment and application of Marfey’s reagent and analogs in enantioseparation: a decade’s perspective

“…The ( S )‐enantiomer of Flx is six times more potent than the ( R )‐enantiomer (Wong, Fuller, & Robertson, 1990). Different methods and reagents used for LC enantioseparation of Flx (both by direct and by indirect approaches) have recently been reviewed in detail by Sethi and Bhushan (2020).…”

“…The (S)-enantiomer of Flx is six times more potent than the (R)-enantiomer(Wong, Fuller, & Robertson, 1990). Different methods and reagents used for LC enantioseparation of Flx (both by direct and by indirect approaches) have recently been reviewed in detail bySethi and Bhushan (2020). (RS)-Fluoxetine was derivatized with MR and FDNP-L-Met-NH and the diastereomeric derivatives so obtained were separated by RPHPLC(Bhushan & Agarwal, 2010).…”

Enantioselective HPLC analysis of escitalopram oxalate and its impurities using a cellulose‐based chiral stationary phase under normal‐ and green reversed‐phase conditions

“…As a rule of thumb, the correct integration of two adjacent nonequimolar peaks requires a reversed enantiomer elution order. To overcome these problems, alternative analytical approaches utilizing different CSPs have been published [3]. The methods available in the literature for the enantioseparation of CIT are based on different types of selectors such as cellulose tris(3-chloro-4-methylphenylcarbamate) [4], amylose tris(3,5-dimethylphenylcarbamate) [5], α l -acid glycoprotein [6], phenylcarbamated β-cyclodextrin [7], cellulose F I G U R E 1 Structures of escitalopram oxalate (ESC) and its chiral impurities A, B, C, H, and K tris(3,5-dimethylphenylcarbamate) [8][9][10], and cellulose tris(phenylcarbamate) [11].…”

Toxicological Study on Chiral Fluoxetine Exposure to Adult Zebrafish (Danio rerio): Enantioselective and Sexual Mechanism on Disruption of the Brain Serotonergic System

“…1 Consequently, selective serotonin reuptake inhibitor (SSRI) antidepressants are among the most common drugs being prescribed. 2 Fluoxetine (FX), the main active ingredient in Prozac, has globally become one of the most widely prescribed SSRI antidepressants. 3 After administration, the unaltered excretion of FX in urine flows into wastewater treatment plants.…”

“…According to the World Health Organization, >300 million people worldwide are experiencing depression . Consequently, selective serotonin reuptake inhibitor (SSRI) antidepressants are among the most common drugs being prescribed . Fluoxetine (FX), the main active ingredient in Prozac, has globally become one of the most widely prescribed SSRI antidepressants .…”