Validation of an HPLC method on short columns to assay ketoconazole and formaldehyde in shampoo

An HPLC method to determine simultaneously ketoconazole and formaldehyde in an anti-dandruff shampoo, originally developed on a long column, was transferred to two short columns with similar stationary phase properties, but with a length of at the most 30% of the initial one. Using the conventional column as reference, the fast HPLC methods on the short columns were validated. The validation characteristics consisted of selectivity, linearity range, precision (repeatability and time-different intermediate precision), bias and robustness. For the ketoconazole assay, linearity for peak area was found in the concentration range up to 0.20 mg/ml. For formaldehyde, two calibration ranges (0-10 x 10(-5) and 0-10 x 10(-4)%) were linear, both for peak area and height. The assays for both ketoconazole and formaldehyde in these ranges showed no bias and an acceptable precision, although the precision found with the short columns was slightly worse than with the long one. The robustness tests were performed applying a Plackett-Burman design. For the ketoconazole assay, 6 factors were examined in a 12 experiments design and for formaldehyde, 11 factors in 16 experiments. The methods were found to be robust. Despite the somewhat less good precision the transfer seems to be successful and the obtained assays on the short columns are applicable for fast routine analysis.