Are you observing the same problem at negative ESI with the scanning problem? It seems to me as an electronic problem you may try to restart the electronics of the MS system. Surely it is a kind of acquisition problem rather than LC.

Have you ever asked to service for supplemental information? They may provide a performance or tuning solution for resolution and signal optimization and you can check the system with these solutions. It could be resulting due to mass filter, ion entrance parameters during scan mode and they should be re-adjusted with the use of the aforementioned solutions. Check the Quad parameters between the scan and MRM modes...If you identify the same problem within these applications, definitely you should consult a technical service for further hardware troubleshooting.

Emir

Hi Michael,

that looks like a pretty unstable spray, what flow rate are you using? I assume you can run some standards and get the kind of data you expect? If not, this is clearly the place to start. The first thing I would do is stabilise the spray, run some standards and take it from there…

Peter G Hains

Hi Peter,

Can you elaborate what you mean by unstable spray? I am running a 0.5mL/min total flow with a gradient from 45% MeOH to 98% MeOH.

When operating in MRM mode I can observe defined peaks for analytes of interest, see attached examples:

Some of these peaks are notably jagged, however other methods I have seen better peak shape for. Is this indicative of a hardware problem?

Thanks,

Michael Knapp

Hi Michael,

if you look at the PDF from your first post, you are getting the TIC varying from 10xe6 to 10xe7, that is massive variance and it needs to be sorted. To me this means the spray is unstable, I’d look for “spitting” of the spray. Is the probe clean, is the electrode still working well, is the flow stable from the LC, are there any leaking connections?

It *may* be a hardware issue, but I’d look for simple solutions first. When I’ve seen this, it’s either been a poorly regulated flow from the LC, or the electrode has needed to be replaced. Bubbles can be an issue, but since you are running at 0.5 mL/min, that should be less of an issue. Regardless, ensure the pumps are properly primed and buffers degassed.

Your recent MRM reaffirms my belief you have a spray issue, especially the TNT pair, the peak shows clear signs of “sawtoothing” which indicates an unstable spray to me. The NGua2 has a hint, but it’s not clear by any means.

See the PDF I’ve attached. The TIC shows small changes over the early phase of the run. Yes, it’s jumping about a bit, but not by an order of magnitude. I’ve then got two MRM pairs, neither are great in terms of points across the peak (not quite enough), but they show no signs of an unstable spray. In all cases this is the raw data, no fancy data smoothing.

Good luck,

Peter