Enantioselective Separation and Determination of Citalopram Enantiomers in Pharmaceutical Dosage Form and Bulk Drug Using Experimental Design Approach on Chiralcel® OC as a Chiral Stationary Phase

An enantioselective HPLC method was developed and validated for the separation and the estimation of citalopram (CIT) enantiomers in bulk drug and pharmaceutical preparations. The method was validated for its linearity (correlation coefficient = 0.9994 and 0.996 for S-(+)-enantiomer and R-(-)-enantiomer, respectively), accuracy, robustness, and intermediate precision. Experimental design was applied during intermediate precision (full factorial 2(3) design) and robustness testing (Box Benken as a factorial design), for robustness test three factors were considered: percentage of organic modifier, flow rate, and temperature. The separation was achieved on cellulose tris(phenylcarbamate) known as Chiralcel (R) OC (25 cm, 4.6 mm i.d.) derivatized cellulose (phenyl carbamate), with UV detection at 245 nm using n-hexane-isopropanol-diethylamine (85:15:0.2, v/v/v) as mobile phase at flow rate 0.7 mL min(-1). A decrease in the flow rate results in decreasing the selectivity factor (alpha), while varying the percentage of n-hexane and the temperature have no effect on selectivity factor (alpha). For intermediate precision, the variables considered were analyst, equipment, and day. The RSD% value (0.73%, n = 24) indicates a good precision for the analytical procedure. The method was found to be suitable for determination of enantiomeric purity of CIT in bulk drugs and pharmaceutical formulations.