A VALIDATED CHIRAL RP-HPLC METHOD FOR THE ENANTIOMERIC SEPARATION OF DULOXETINE HYDROCHLORIDE USING CHIRAL-AGP AS THE STATIONARY PHASE

Abstract

The present paper describes the development and validation of chiral HPLC method for the enantiomeric separation of Duloxetine hydrochloride [(S)-N-Methyl-3-(1-naphthalenyloxy)-3-(2-thienyl)propanamine], an antidepressant drug. The enantiomers of Duloxetine hydrochloride were baseline resolved on a Chiral-AGP (150 mm × 4.0 mm, 5 µm) column using a mobile phase consisting of acetate buffer (pH 3.8; 10 mM)-acetonitrile (93:07, v/v) at a flow rate of 1.0 mL/min. Interestingly, distomer was eluted prior to eutomer in the developed method. The optimum conditions of resolution were established by systematically studying the effect of organic modifier, pH of buffer, concentration of buffer, and column temperature. The thermodynamic parameters were also calculated. The developed method was extensively validated. Thus, the limit of detection and limit of quantification of (R)-enantiomer were found to be 150 and 400 ng/mL, respectively, for 5 µL injection volume, whereas the method precision for (R)-enantiomer at limit of quantification level was within 1.4% RSD. The recovery of (R)-enantiomer was within 105% in bulk drug. The proposed method was found to be suitable, precise, and accurate for the quantitative determination of (R)-enantiomer in bulk drugs as well as in pharmaceutical formulations.