Bacterial Endotoxins Testing of Water-Insoluble Drug Substances by Means of Dispersion with Dimethyl Sulfoxide

摘要

Active pharmaceutical ingredients are often poorly soluble in water. The detection of bacterial endotoxins in such substances requires a homogeneous aqueous suspension, which presents difficulties in ensuring uniform dispersion of the sample through the mixture. We demonstrate a technique for sample preparation in which the drug substance is dissolved in dimethyl sulfoxide (DMSO), followed by dilution in water. This results in a more uniform suspension than can be achieved by direct addition of sample to water. This method allows testing for endotoxins via the chromogenic technique,.which results in a 15-fold increase in method sensitivity compared to the gel-clot technique. The increased sensitivity allows for testing of higher sample dilutions, increasing the likelihood that sample interference can be overcome.