Chromatography Forum

What're the downsides of injecting high concentration salt solution into ESI QTOF? I am seeing sudden decrease of resolution just after LC run is started. Because the might have high amount of salts, and the main analyte doesn't bind to the column, I'm not able to divert the initial eluent to waste.

This is also evident by the fact that during blank run, I don't see any loss of resolution just after the injection.

I'm guessing that if your target analyte is going into the MS at the same time as a lot of salt, then you have a horrible choice of either enduring nasty space-charging effects (where you let a lot of ions in, they all repel one another, and as a result instead of getting a nice neat package of ions travelling down the flight-tube, they expand to a fuzzy blob), or enduring very small signals (by putting a lower total number of ions into the system, but this meaning that a very very low number of ions are actually the target analyte).

Generally, if your main analyte isn't retained, it's time to change to a different mode of chromatography. If you're doing reverse phase, have you considered Hilic?

Thanks for your suggestion. I'll check with Hilic