Chromatography Forum

UPLC-MS/MS (Waters Xevo TQD)
Atlantis Premier BEH Z-HILIC column
Ammonium bicarbonate based mobile phases with ACN
Running at 0.5 mL/min to 0.9 mL/min


I have run a sample list as per my normal protocol but after the first blank the instrumentation shuts down due to exceeding the 15,000 psi pressure.
I have run a dynamic leak test for both pump A and B as well as the accumulators with no leaks detected.
I have been playing around flow rate and mobile phase percentages and it seems that mobile phase B can be as high as 95% with a flow rate of 8 mL/min with a stable psi of maximum 14,000 (as expected) with the normal flow rate of 0.5 mL/min at the expected 11,000 psi.
Mobile phase A can only be run at 95% flow rate at a maximum of 0.4 mL/min before reaching 17,500 psi.
I can run at a higher flow rate of 1 mL/min as long as mobile phase A is >50%.

I have run samples at the beginning of the week with no issues but upon changing mobile phase B on Wednesday, these problems have began with mobile phase A.
Does anyone have any ideas as to what is causing the sudden and random issue?

I assume you have different solvents in A and B? If so, it's quite normal to get different pressures with the different solvents.

If you've got exactly the same solvent on A and B, but wildly different pressures, then something has gone wrong. You've probably either got a bottle that doesn't contain what you think it does, or you've precipitated something in one of them (e.g. by cross-contamination from whatever they were in before).