Development and Validation of a HPLC Method for Determination of Potential Residual Cortisone Compounds in Timolol Maleate Eye Drops

摘要

One way of ensuring effective cleaning in the pharmaceutical industry is to analyze the batch of a product for a potential carry over contamination from a previously manufactured one. The potential cross contamination of timolol maleate (TM) eye drops with cortisone compounds, deserves special consideration, due to the well known deleterious effect of cortisones on glaucoma. Therefore, it was the objective of this study to develop and validate a HPLC method for the detection and quantitative determination of cortisones in TM eye drop preparations. The chromatographic behaviors of the five cortisones that were most likely to be present as contaminants in TM eye drops were characterized on different HPLC stationary phases (normal silica, Qg, C8, and CN). Mobile phase and buffer constituents were further optimized on the best stationary phase material (C18). The final recommended mobile phase consisted of a mixture of THF-methanol:0.01M phosphate buffet at ratios of 15:25:60 and containing 0.01 M camphoresulfonic acid (pH adjusted to 4.2). The method was validated in light of ICH guidelines and applied to commercial samples with satisfactory results.