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 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.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania.
Melania
M
Cârcu-Dobrin
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania.
Monica
M
Budău
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania.
Gabriel
G
Hancu
SC VimSpectrum SRL, Tîrgu Mureş, Romania.
Laszlo
L
Gagyi
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania.
Aura
A
Rusu
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Medicine and Pharmacy of Tîrgu Mureş, Tîrgu Mureş, Romania.
Hajnal
H
Kelemen
Capillary electrophoresis; Chiral separation; Cyclodextrines; Fluoxetine; Selective serotonin reuptake inhibitor