The USP referenced mobile phases for Organic Impurities, Procedure 1 requests dibasic sodium phosphate and tertiary butyl alcohol mixed with methanol. The reproducible premixing of eluents consisting of three different components is generally challenging. The consistent composition of the mobile phases from batch to batch might be questionable. In addition, these eluents are not MS-compatible, are prone to salt precipitation, and are inconvenient for the preparation. Specifically, the tertiary alcohol has a melting point of 25 °C, which makes it difficult to handle at room temperature. For these reasons, the described eluents might not be ideal for running routine methods with high eluent consumption. Here, the mobile phase was changed to an MS-compatible 25 mM ammonium acetate buffer, pH 3.8, as eluent, mixed with methanol and acetonitrile by the quaternary pump. The literature method uses a 250 mm long column with 5 μm fully porous particles and applies gradients between 60 and 70 minutes for organic impurity profiling. To decrease the method run time, a 100 mm, 2.6 μm fused core column is used.