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® octadecylsilyl 1 column (5.0 μm particle size, 250 × 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°C. The buffer was 0.05 M KH 2PO4 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.