LC determination and purity evaluation of nefazodone HCl in bulk drug and pharmaceutical formulations.

A simple, selective and reproducible reversed-phase liquid chromatography (LC) method has been developed for the quantitative determination of nefazodone hydrochloride (I) in the presence of its related impurities, namely 5-ethyl-4-(2-phenoxyethyl)-2H-1,2,4-triazol-3-(4H)one (II), 1-(3-chlorophenyl)-4-(3-chloropropyl) piperazine hydrochloride (III) and 1,1(1)-trimethylene-bis[4-(3-chlorophenyl) piperazine] hydrochloride (IV). The separation was achieved using an Inertsil ODS-3V (250 x 4.6 mm(2)) column and a mobile phase comprising 0.05 M KH(2)PO(4) (pH 3.0), acetonitrile and methanol in the ratio 50:40:10 (v/v/v). The method has been completely validated and proven to be rugged. The limit of detection and limit of quantification for impurities II, III and IV were found to be 50, 79 and 91 ng/ml, and 152, 240 and 280 ng/ml, respectively. The intra- and inter-day assay precision of the method was within 1.2% relative standard deviations. The developed method was applied to the pharmaceutical dosage form (Tablet, Serzone-R) and the percentage recoveries ranged from 99.1 to 100.7. The percentage recovery of impurities ranged from 96.2 to 108.9. The stability studies were performed for nefazodone solution placed on laboratory bench and in the refrigerator for 60 days. The method was proved to be stability indicating in solution.