Development and Validation of an HPLC Method for Determination of Ziprasidone and Its Impurities in Pharmaceutical Dosage Forms

Abstract

Ziprasidone is known as a novel "atypical" or "second-generation" antipsychotic drug. A sensitive and reproducible method was developed and validated for determination of ziprasidone and its major impurities, which are significantly different in polarity. The separation is performed on a Waters Spherisorb (R) octadecylsilyl 1 column (5.0 mu m particle size, 250 x 4.6 mm id) using a gradient with mobile phase A [buffer acetonitrile (80+20, v/v)] and mobile phase B [buffer acetonitrile (10+90, v/v)] at a working temperature of 25 degrees C. The buffer was 0.05 M KH(2)PO(4) solution with an addition of 10 mL triethylamine/L solution, adjusted to pH 2.5 with orthophosphoric acid. The flow rate was 1.5 mL/min, and the eluate was monitored at 250 nm using a diode array detector. Optimization of the experimental conditions was performed using partial least squares regression, for which four factors were selected for optimization: buffer concentration, buffer pH, triethylamine concentration, and temperature. The proposed validated method is convenient and reliable for the assay and purity control in both raw materials and dosage forms.