Quantitative Analysis of Duloxetine and 1-Naphthol by Capillary Micellar Electrokinetic Chromatography

Nathalie      R. Wingert; Aline      B. Barth; Patricia      Gomes; Elfrides      E. S. Shapoval; Martin      Steppe

Abstract

Duloxetine (DLX) is a selective orally administered serotonin and norepinephrine reuptake inhibitor usually used in the treatment of major depressive disorder. 1-Naphthol (NPH) is a toxic impurity produced when DLX is exposed to acid medium and it also proceeds from the synthesis material. A simple and rapid stability indicating capillary micellar electrokinetic chromatography method was developed and validated for the simultaneous analysis of DLX and NPH, using cimetidine as internal standard. The method was performed with a fused-silica capillary with applied voltage of 25 kV. The background electrolyte consisted of 50 mM Tris and 20 mM SDS, pH 10.6. The linear calibration range was 50-550 μg.mL-1 for DLX and 0.55-5.5 μg.mL-1 for NPH, with r=0.9999 for both molecules. The limits of detection and quantification were 0.50 and 1.45 μg.mL-1 for DLX and 0.20 and 0.55 μg.mL-1 for NPH, respectively. The performed degradations were: acid and basic media with 0.1 M HCl and 1 M NaOH, respectively, oxidation with 6 % H2O2 (v/v), temperature at 60 °C and the exposure to UV light. No interference in the DLX migration was verified. Adequate results for accuracy, precision, selectivity and robustness were obtained. The proposed method was successfully applied for the simultaneous quantitative analysis of DLX and NPH. The DLX data were compared to those obtained by a validated reversephase liquid chromatography method, showing non-significant differences between them. The developed method may be applied to routine quality control of DLX and to assure that NPH does not exceed the allowed amounts.

Keywords: 1-naphthol, Duloxetine, Impurity, MEKC, Degradation product, Simultaneous analysis of drugs, Norepinephrine reuptake inhibitor, Serotonin reuptake inhibitor, Reversephase liquid chromatography, Capillary electrophoresis