The ultra-performance liquid chromatography determination of domperidone and its process-related impurities.

A rapid ultra-performance liquid chromatography (UPLC) method for the determination of domperidone in the presence of its process impurities and droperidol was developed and validated. The rapid chromatographic separation was achieved using a sub 2 µm Hypersil Zorbax eXtra Densely Bonded C18 column (30 × 4.6 mm, i.d., 1.8 µm). A gradient mobile phase consisting of Solvent A: 0.06 M ammonium acetate and Solvent B: methanol, with a flow rate of 1 mL/min was employed. The column temperature was set at 40°C, and the diode-array detector was set at 280 nm. An injection volume of 3 µL was used. The currently utilized European Pharmacopeia (Eur. Pharm.) method employed by Janssen Pharmaceuticals Ltd was run on a Hypersil Base-Deactivated Silica C18 column (100 × 4.6 mm, i.d., 3 µm) with a run time of 12.5 min. The developed UPLC method, with a run time of 7.5 min was determined to be accurate, precise, specific, robust and highly sensitive according to the International Conference on Harmonization guidelines. The method herein demonstrated a reduction in analysis time of 40%, allowing for a much higher sample throughput. A solvent consumption decrease of over 58% was also observed, which results in a dramatic reduction in running costs for Janssen Pharmaceuticals Ltd.

Development and validation of a rapid liquid chromatographic method for the determination of oxatomide and its related impurities.

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.