Ruggedness tests were performed on the United States Pharmacopoeia assay for tetracycline.HCl to examine problems previously reported in the literature. The experiments were performed on nine different columns. The effects of four factors selected from the procedure were examined on qualitative responses by performing half-fraction factorial designs at three different ages on each column. The influence of column ageing was separately evaluated by injections under nominal method conditions at different ages. The C-8 columns gave a separation that was as good as, or better than, the C-18 ones and were less influenced by ageing. The normalized effects of each of the factors on a response were compared and found to be more or less equal for most of the columns and to remain constant with time. The responses were most affected by the pH of the mobile phase and by the content of the organic modifier. In general it was found that C-8 columns were preferred for this assay