Maximizing the peak capacity using coupled columns packed with 2.6 μm core–shell particles operated at 1200 bar

We report on the peak capacity that can be produced by operating a state-of-the-art core–shell particle type (dp = 2.6 μm) at its kinetic optimum at ultra-high pressures of 600 and 1200 bar. The column-length optimization needed to arrive at this kinetic optimum was realized using column coupling. Whereas the traditional operating mode (using a single 15 cm column operated at its optimum flow rate of 0.4 mL/min) offered a peak capacity of 162 in 10.8 min, a fully optimized train of 60 cm (4 × 15 cm) columns offered a peak capacity of 325 in 61 min when operated at 1200 bar. Even though the particles have a reputed low flow resistance and a relatively large size (>2 μm), it was found that the increase in performance that can be generated when switching from a fully optimized 600 bar operation to a fully optimized 1200 bar operation is significant (roughly 50% reduction of the analysis time for the same peak capacity and approximately a 20% increase in peak capacity if compared for the same analysis time). This has been quantified in a generic way using the kinetic plot method and is illustrated by showing the chromatograms corresponding to some of the data points of the kinetic plot curve.

► Use of 2.6 μm core–shell columns operated at 1200 bar in gradient UHPLC.
► Coupling columns are needed to operate at the kinetic optimum at this pressure.
► Increased pressure results in a substantial gain in performance or analysis time.
► Even 2 μm particles can benefit from a 1200 bar operation limit.