UHPLC-MS vs. HPLC-MS

[parkc23]

Hi,
As the front end for single Q MS, which one would be better between UHPLC and HPLC? and what would be the reason?
Thanks.

[tom jupille]

In favor of the UHPLC:
- Lower volumetric flow rates
- Faster throughput
- Lower extra-column volume
- Smaller dwell (gradient delay) time
- Smaller columns (so less dilution of sample, so somewhat better sensitivity)

In favor of the HPLC
- Less demanding in terms of lab technique, sample cleanup, filtration, etc.

[parkc23]

Thanks, Tom.
Among the points you mentioned for the UHPLC, which one provides significant advantage for MS compared to HPLC?

For HPLC, less demanding lab techniques was counted as an advantage. What I was told from UHPLC sale rep was that UHPLC can be handled as easy as HPLC these days. Does UHPLC really require such a strict handling relative to HPLC?
Thanks.

[lmh]

A lot depends on your work-flow and business situation. If you need to get through lots of samples fast, then UPLC has big advantages. It is true that it is easier nowadays; finger-tight UPLC fittings really do work now. If you are nervous of blocking 1.7u columns with dirty samples, it is also possible to use solid core columns, which offer many of the advantages of small particle columns, but at pressures associated with larger particles. In theory these work on conventional systems, but they benefit from all the optimisation carried out by manufacturers of UPLC systems (low dead volumes, fast injection cycles etc.). Also the solid-core columns of some manufacturers, in some formats, are actually UPLC-pressure tolerant (for example 2mm diameter Kinetex columns from Phenomenex), which potentially allows very short runs.

Another thing that matters is whether you need high resolution. If you have peaks that are just that little bit too uncomfortably ill-resolved, where the extra root-2 of doubling column length would be nice, but pressure is holding you back, UPLC will make it possible.

I would always choose to have the capability of UPLC if I could - you don't have to use it all the while.