On-line sample enrichment system coupled to electrospray ionization time-of-flight mass spectrometry (ESI–TOF–MS)

In order to enhance the sensitivity of LC–MS, a novel on-line sample enrichment system was integrated by inserting a column-switching device containing a peak parking loop after conventional LC column and UV detector. The system consists of conventional LC, micro-LC, a parking loop, and a micro-precolumn, all connected through one eight-port switching valve. An analyte peak of interest detected on the conventional LC is stored in the parking loop with an appropriate amount of added water. The analyte is then directly transferred to the micro-precolumn to be concentrated, and then eluted from the precolumn with linear gradient and separated by the micro-LC column. The sensitivity of LC–MS can be increased by a factor of up to a 100. By combining the micro-LC column with ESI–TOF–MS, some structural information including accurate molecular weight were obtained from analyte samples in the pmol range.