Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis

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 s...

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Main Authors: Melania Cârcu-Dobrin, Monica Budău, Gabriel Hancu, Laszlo Gagyi, Aura Rusu, Hajnal Kelemen
Format: Article
Language:English
Published: Elsevier 2017-03-01
Series:Saudi Pharmaceutical Journal
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1319016416300998
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author Melania Cârcu-Dobrin
Monica Budău
Gabriel Hancu
Laszlo Gagyi
Aura Rusu
Hajnal Kelemen
author_facet Melania Cârcu-Dobrin
Monica Budău
Gabriel Hancu
Laszlo Gagyi
Aura Rusu
Hajnal Kelemen
author_sort Melania Cârcu-Dobrin
collection DOAJ
description 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.
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spelling doaj.art-22a81ceb7e91411791f240a3111621892022-12-22T02:43:35ZengElsevierSaudi Pharmaceutical Journal1319-01642017-03-0125339740310.1016/j.jsps.2016.09.007Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresisMelania Cârcu-Dobrin0Monica Budău1Gabriel Hancu2Laszlo Gagyi3Aura Rusu4Hajnal Kelemen5Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, RomaniaSC VimSpectrum SRL, Tîrgu Mureş, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, RomaniaDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, RomaniaFluoxetine 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.http://www.sciencedirect.com/science/article/pii/S1319016416300998FluoxetineSelective serotonin reuptake inhibitorCapillary electrophoresisChiral separationCyclodextrines
spellingShingle Melania Cârcu-Dobrin
Monica Budău
Gabriel Hancu
Laszlo Gagyi
Aura Rusu
Hajnal Kelemen
Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
Saudi Pharmaceutical Journal
Fluoxetine
Selective serotonin reuptake inhibitor
Capillary electrophoresis
Chiral separation
Cyclodextrines
title Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
title_full Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
title_fullStr Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
title_full_unstemmed Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
title_short Enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
title_sort enantioselective analysis of fluoxetine in pharmaceutical formulations by capillary zone electrophoresis
topic Fluoxetine
Selective serotonin reuptake inhibitor
Capillary electrophoresis
Chiral separation
Cyclodextrines
url http://www.sciencedirect.com/science/article/pii/S1319016416300998
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