2019 PharmSci 360
Impurities in an API can significantly affect stability, efficacy, and patient safety. Especially if the impurity is toxic in nature, it places a higher burden on the method sensitivity in various matrices combined with limited availability of reference standard. In this case study we explore the synthesis of amino-drug intermediates prepared via the reduction of aromatic nitro groups to the corresponding amines. A comparison of the response factors for structural analogs containing nitroso, hydroxyamine, azoxy, amino and nitro groups was performed as a means to determine the accuracy of relative quantitation, as this approach is commonly used due to the lack of commercially available standards of these impurities. The resulting amino-drug intermediates were characterized using Quadrupole Time of Flight Gas and Liquid Chromatography Mass Spectrometry (QTOF-GCMS and QTOF-LCMS) to identify potential mutagenic impurities and method for quantitation was developed and validated on triple quadrupole liquid chromatography mass spectrometry (QqQ-LCMS).