Capillary electrophoresis method for the determination of (R)-dapoxetine, (3S)-3-(dimethylamino)-3-phenyl-1-propanol, (S)-3-amino-3-phenyl-1-propanol and 1-naphthol as impurities of dapoxetine hydrochloride

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A capillary electrophoresis method was developed and validated for the determination of the purity of dapoxetine with regard to the related substances (3S)-3-amino-3-phenylpropan-1-ol, (3S)-3-(dimethylamino)-3-phenylpropan-1-ol, 1-naphthol and the enantiomer (R)-dapoxetine. The separation was based on a dual selector system, which was optimized by a fractional factorial resolution V + design followed by a central composite face centered design with star distance 1 and Monte Carlo simulations for defining the design space. The optimized background electrolyte consisted of a 50 mM sodium phosphate buffer, pH 6.3, containing 45 mg/mL sulfated γ-cyclodextrin and 40.2 mg/mL 2,6-dimethyl-β-cyclodextrin. Separations were carried out in a 23.5/32 cm, 50 μm fused-silica capillary employing a separation voltage of 9 kV at 15 °C. Following robustness testing using a Plackett-Burman design the method was validated according to the International Council on Harmonization guideline Q2(R1) in the range of 0.05–1.0% relative to the dapoxetine concentration. The method was applied to the analysis of drug substance and a commercial tablet. Data regarding the enantiomeric purity of dapoxetine obtained by the capillary electrophoresis assay were comparable to the data obtained by an enantioselective HPLC method.HighlightsValidated method for purity determination of dapoxetine.Simultaneous determination of enantiomer and related substances.Application of analytical quality by design in method development.Application to the analysis of drug substance and tablets.

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