Optimization of mobile phase by 32-mixture design for the validation and quantification of risperidone in bulk and pharmaceutical formulations using RP-HPLC

Abstract

A rapid, sensitive and optimized reversed phase-HPLC method has been developed for routine analysis of risperidone in bulk drugs and pharmaceutical formulations with UV detection at 238 nm. Chromatographic separation was performed on a Hypersil ODS C-18 column (250 × 4.6 mm, i.d., 5 μm particle size) with isocratic elution of the mobile phase containing a mixture of methanol–acetonitrile–phosphate buffer (0.02 M) (65 : 20 : 15, v/v/v) with a flow rate at 1.0 ml min⁻¹ and pH 3.0. A 3² mixture design methodology was employed for the optimization and validation of the mobile phase components for a high degree of robustness i.e., peak area and retention time. The optimum mobile phase composition was a trade-off between the experimental design by graphical optimization of the technique using an overlay plot. Further, the method was validated as per the ICH guidelines using linearity, accuracy, precision, sensitivity, system suitability and selectivity as the parameters. The developed method was found to be simple, sensitive, and highly robust for routine analysis of risperidone.