Rapid liquid chromatographic determination of itraconazole and its production impurities.

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.