Chromatographic Method Development for Separation of Halogenated Anilines

Halogenated anilines are common precursors to the synthesis of active pharmaceutical ingredients (APIs). Controlling impurities in the precursors is crucial to ensuring high API quality, but this is challenging due to similarly structured impurities. Current methods exist for a few targeted compounds, but offer limited applicability during route development. Previously, a gas chromatography-flame ionization detector (GC-FID) method was developed to separate a number of these anilines, but it provided no resolution on others. High performance liquid chromatography (HPLC) is a common separation tool used in analytical chemistry with more controllable parameters that impact analyte separation compared to GC. We developed and optimized an HPLC method that would be able to resolve a majority of similarly structured halogenated anilines as well as establish a reliable and broadly applicable method for a wide range of halogenated anilines. During this process, we also explored the relationship between analyte properties and retention times with a variety of columns.