Development of rapid methods for quality control of X-ray agnets by high-performance liquid chromatography

Abstract

The background for this thesis was to test some of the new column materials and columns in order to find suitable column for quality control of Omnipaque and Visipaque x-ray agent products. Focus was on the columns packed with small particles, columns specially suited for analysis of polar compounds and columns composed of in-place-synthesized monolithic materials. After preliminary testing, two columns, the Aqua and Chromolith Performance columns, were chosen for further development and validation of new methods. Both isocratic and gradient elution were to be explored to find the optimum conditions, as well as influence of the temperatures variations on the separation and analysis time.

Experimental work showed that with so-called stepwise gradient elution programs could requirements for quality control of mentioned X-ray products be satisfied. This included the separation of Iohexol/Iodixanol isomers and their separation from other impurities present in the Omnipaque/Visipaque final products. A two-step gradient program, from 3% to 7% acetonitrile in water in time range of 10 minutes, was used to analyse Omnipaque injection solutions using the Aqua or Chromolith Performance column. Analysis of Visipaque bulk solutions using the Chromolith Performance column was carried out with stepwise gradient program, where in the first step the amount of acetonitrile in water was held at 8% in 10 minutes before increase to 25% where it was held in 5 minutes. When analysing Visipaque bulk solution on the Aqua column, the gradient program consisted of two steps, where in the first step the amount of acetonitrile was held constant at 9% in 8 minutes and than in the next step at 25% in 7 minutes.

Changes in operational temperature did not provide any decrease in the retention times or improvements in the separation of the compounds of interest. Both, the Aqua column and the Chromolith Performance column showed similar performance and are good alternatives for control of Omnipaque/Visipaque products.

Keywords; Omnipaque, Visipaque, small particles, polar compounds, monolithic materials, stepwise gradient elution