title: Chiral recognition of dapoxetine enantiomers with methylated-gamma-cyclodextrin: a validated capillary electrophoresis method.
abstract: The enantiomers of dapoxetine, a serotonin transporter inhibitor for the treatment of premature ejaculation have been separated by cyclodextrin modified capillary zone electrophoresis using uncoated fused-silica capillary. Over 20 cyclodextrins were screened as chiral selectors, investigating the stability of the inclusion complexes and enantioseparating properties. According to the preliminary experiments as chiral selector randomly methylated-γ-cyclodextrin was chosen. The basic chemical and instrumental parameters of enantioseparation as concentration of buffer, chiral selector and organic additive, pH, temperature and applied voltage were optimized afterwards using an orthogonal experimental design. Using this methodology not only the optimal parameter values for chiral separation (15 °C, +15 kV, 70 mM acetate, 20 v/v% MeOH, pH*=4.5, 3 mM methylated-γ-CyD) but also the significance order of factors on resolution was determined. Applying these parameters an optimal resolution of 7.01 was achieved. The optimized method was then validated according to the ICH guideline Q2 (R1) with regard to repeatability, linearity range, LOD, LOQ, accuracy and robustness.
authors.affiliation: Semmelweis University, Department of Pharmaceutical Chemistry, Hőgyes Endre u. 9, Budapest H-1092, Hungary.
authors.forename: Gábor
authors.initials: G
authors.lastname: Neumajer
authors.forename: Tamás
authors.initials: T
authors.lastname: Sohajda
authors.forename: András
authors.initials: A
authors.lastname: Darcsi
authors.forename: Gergő
authors.initials: G
authors.lastname: Tóth
authors.forename: Lajos
authors.initials: L
authors.lastname: Szente
authors.forename: Béla
authors.initials: B
authors.lastname: Noszál
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Béni
mesh_terms: D001596:Benzylamines / Q000737:chemistry*; D019075:Electrophoresis, Capillary / Q000379:methods*; D057230:Limit of Detection; D009682:Magnetic Resonance Spectroscopy; D008745:Methylation; D009281:Naphthalenes / Q000737:chemistry*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D001596:Benzylamines; D009281:Naphthalenes; D047408:gamma-Cyclodextrins; C080598:dapoxetine; C023792:gamma-cyclodextrin