A fully automated on-line sample preparation system for LC-MS has been developed for the structural elucidation of compounds in mixtures. The system consists of conventional HPLC for separating the compounds of interest, five parking- loops for parking the separated compounds, two precolumns operating in parallel for purification of the compounds from the parking-loops, and micro LC, connected through six 6-port switching valves, for eluting the compounds from the precolumns. The system allows easy separation of trace amounts of the compounds from the mixture, desalting the concentration of the separated compounds for LC-MS measurements with higher sensitivity. The system was successfully applied to mass measurements of trace amounts of impurities in bulk drug substances as models. This new tool should be of considerable value in a variety of fields where rapid sample preparation for LC-MS measurements with higher sensitivity is desired.
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