Highly sensitive and rapid normal-phase chiral screen using high-performance liquid chromatography–atmospheric pressure ionization tandem mass spectrometry (HPLC/MS)

In the last years, there has been an increasing demand on the development of quantitative assays for determination of enantiopurity. Herein, we present a methodology based on a direct linking of an atmospheric pressure ionization mass spectrometer (MS-APCI) with a high-performance liquid chromatography HPLC (DAD) system, operated under normal-phase mode and without post-column addition of MS-compatible solvents, which provides the high specificity/selectivity (identification of isomers in complex mixtures) and accuracy (1–2% area level) required for daily chiral studies. As result of the success of our screen, the preparation of individual enantiomers or the racemic mixture in our Drug Discovery Research Laboratories at Lilly, Spain is usually not required. Therefore, additional non-valuable synthetic work is eliminated.