ABSTRACT
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.
Subject(s)
Chromatography, High Pressure Liquid/methods , Domperidone/analysis , Domperidone/chemistry , Drug Contamination , Limit of Detection , Linear Models , Reproducibility of ResultsABSTRACT
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.
Subject(s)
Chromatography, Liquid/methods , Piperazines/analysis , Piperazines/chemistry , Drug Contamination , Limit of Detection , Linear Models , Reproducibility of ResultsABSTRACT
A simple, rapid ultra-performance liquid chromatography (UPLC) method was developed for the analysis of itraconazole and its associated production impurities. The optimum chromatographic conditions were achieved using an Agilent Zorbax Eclipse XDB C18 column, 1.8 µm (4.6 × 50 mm) installed in a column oven heater utilizing a gradient mobile phase of 0.08M tetrabutylammonium hydrogen sulfate buffer-acetonitrile (80:20, v/v), with ultraviolet detection at 235 nm. An Agilent 1200 RRLC Series was used for the UPLC analysis. UPLC is a technology that greatly reduces analysis time by utilizing columns packed with sub-2 µm particles. The method was validated according to International Conference on Harmonization guidelines with respect to precision, accuracy, linearity, robustness and limits of detection and quantification. All parameters were found to be well within the stated guidelines. The total analysis time was reduced by two-thirds, from over 30 min (the current European Pharmacopeia method) to under 10 min, and the method is applicable for assay and related substance determination. A method utilizing the sub-2 µm column on a conventional high-performance liquid chromatography system was also developed and validated, resulting in substantial time and solvent savings.
Subject(s)
Chromatography, High Pressure Liquid/methods , Itraconazole/analysis , Itraconazole/chemistry , Limit of Detection , Linear Models , Reproducibility of ResultsABSTRACT
A rapid selective method for the analysis of flunarizine and its associated impurities was developed and validated according to ICH guidelines. The separation was carried out using a Thermo Scientific Hypersil Gold C18 column (50 mm×4.6 mm i.d., 1.9 µm particle size) with a gradient mobile phase of acetonitrile-ammonium acetate-tetrabutylammoniumhydrogen sulfate buffer, at a flow rate of 1.8 mL/min and UV detection at 230 nm. Naturally aged samples were also tested to determine sample stability. A profile of sample and impurity breakdown was also presented.
