Chromatography Forum

We have two Waters UPLC and Xevo TQXS triple quads. LCMS1 has been operating 24/7, LCMS2 hasn't been used for a couple of months, so I'm trying to get LCMS2 back up. Before putting on any samples on LCMS2, I made fresh solvents (water and methanol with formic acid), flushed the whole system with high organics (methanol/IPA mixture), put a new analytical column, cleaned the MS front end/cones, and tuned the MS (positive mode only because we only do ES+).

I ran splits of the same samples on the LCMS2 that were ran on LCMS1 previously, using the same LC and MS methods, but the signal is much lower and the peaks are really jagged. I also ran standards on the LCMS2, but the standard peaks look great (symmetrical, smooth, sharp). I also ran leak tests on LCMS2 to confirm that there were no leaks.

If I didn't have any sample chromatograms from LCMS1, I would have just looked at the LCMS2 data and assumed that the samples were not "clean" enough or the analyte concentrations were too low. But the sample chromatograms from LCMS1 look much better than LCMS2, even though I'm using the same LC and MS methods. What should I be looking for in LCMS2 to improve my peak shapes?


(link for image: https://ibb.co/jHRQDRS)

The sample peaks look similar in shape on both instruments. The main difference I see is the 10 times lower signal-to-noise ratio on LCMS2. It is clear that you need to increase the signal. It is not clear whether the noise is higher on LCMS2 and whether you need to reduce this noise.