Ultra-High Peak Capacity Exceeding 5 Peaks per Second Enabled by LC×LC-SLIM-qTOF-MS for the Analysis of Complex Samples

Comprehensive two-dimensional chromatography substantially enhances separation performance prior to mass spectrometric detection compared to conventional one-dimensional approaches. This results in (i) cleaner and more readily interpretable mass spectra and (ii) reduced ion suppression in atmospheric pressure ionization sources. To further increase separation performance within a reasonable total analysis time, comprehensive LC×LC was coupled to a SLIM-IM-qTOF-MS system for the analysis of complex herbal liqueur samples. To facilitate the processing of multidimensional data, a long modulation time of 4 min was applied. In addition, trap-based modulation was implemented to improve analyte focusing and optimize two-dimensional pre-separation. A peak capacity of LC×LCn = 201 was achieved for the LC×LC separation. Incorporating ion mobility as a third separation dimension further increased the total peak capacity. Total peak capacities of Ptotal(SLIM) = 16,683 and Ptotal(DTIMS) = 8643 were achieved for the SLIM and DTIMS coupling, respectively. The SLIM coupling therefore provided an approximately 1.9-fold higher total peak capacity than the DTIMS coupling, demonstrating its superior separation potential.