Structural analysis of impurities in pharmaceutical ingredients using trap-free 2D-LC high-resolution accurate mass spectrometry

High performance liquid chromatography (HPLC) is the primary means for impurity testing in pharmacopeia. Solutions containing non-volatile salts are frequently used as a mobile phase because of the irreplaceable advantage to achieve better chromatographic performances. However, non-volatile mobile phases are not compatible with mass spectrometry which is commonly used for structural analysis of impurities. Trap-free two-dimensional HPLC (trap-free 2D-LC) can fill this gap by exchanging a non-volatile mobile phase with a volatile one compatible for mass spectrometry.
In this study, we demonstrate how structural analysis of impurities in pharmaceutical ingredients is feasible by using trap-free 2D-LC coupled to quadrupole time-of-flight mass spectrometry (QTOF MS) without modifying the original method mobile phases.