Development and Validation of a Rapid Liquid Chromatographic Method for the Determination of Oxatomide and Its Related Impurities

Abstract

A rapid liquid chromatographic method was developed for the determination of oxatomide in its finished active pharmaceutical ingredient form and in the presence of its process impurities. The method was developed on a sub 2 µm Hypersil Zorbax XDB C18 column (30 × 4.6 mm, i.d., 1.8 µm). The rapid method employed a gradient mobile phase consisting of solvent A: 0.01 M tetrabutylammonium hydrogen sulfate and 0.5% (w/v) ammonium acetate in water and solvent B: acetonitrile. A flow rate of 2 mL/min was employed with the diode-array detector set at 230 nm. The original method supplied by Janssen Pharmaceuticals Ltd was run on a Thermo Scientific octadecylsilyl silica gel C18 column (100 × 4.6 mm, i.d., 5 µm) with an analysis time of 20 min. The main aim was to substantially reduce the analysis time while maintaining good efficiency. Run-time was reduced to 6.5 min with a total loss in analysis time of 68%. Solvent consumption was also reduced by 68%. Validation according to the International Conference of Harmonization guidelines was undertaken. The parameters examined were accuracy, precision, linearity, selectivity, robustness, limit of detection and limit of quantification; all criteria were met. Sample stability testing was also carried out. Oxatomide proved stable under ambient and 4°C temperatures and in the presence of light for up to 24 h.