Replacing Ecologically Risky Trifluoroacetic Acid and Acetonitrile With Methanesulfonic Acid and Dimethyl Carbonate in High‐Performance Liquid Chromatography Analyses of Small Molecule Drugs

O and 0.1 parts MSA was found to be equivalent to ACN containing 0.1% TFA. By employing a reproducible protocol using EtOH as a co-solvent, we were able to overcome current challenges associated with the use of organic carbonates in HPLC, which primarily arise from their limited miscibility with water. Given the continued widespread use of gradient HPLC methods employing ACN as an eluent and TFA as an acidic modifier, the methods presented herein offer significant potential to advance the implementation of sustainability in pharmaceutical quality control and medicinal chemistry.