Hi, Friends

I need an urgent help. How do you obtain a smooth baseline in LC/MS? I am using 50:50, acetonitrile:water as a blank, and the baseline shows a constant trend but very broad and very dark as if there are too many peaks very close to each other.

Hello Friends,

Need your help ASAP! I have problem with ghost peaks on a very smooth baseline of a gradient run. After a blank 50% acetonitrile-water injection of 10 uL or 0 uL, the base line shows 2 peaks at the two m/z ratios of the drugs of interest, even on a brand new column. The peaks were gone when a union replaced the column. This problem happened with unknown reason right after the system was pre-validated and ready for a full validation of the 2 drugs of interest, artesunate and dihydroartemisinin. Before the problem occured, the baseline started flat at the beginning of the injection for ~ 4 mins and slowly rised up becoming a plateau in the region where the peaks of interest came out until the end of run (~ 8 min).

When the problem occured, the baseline had less noise, the plateau was gone and the 2 peaks showed up. It looked like the plateau covered up the peaks of interest. We suspect that the change in the baseline is related to electronic problem.

It sounds as if your solvents are contaminated. Even as specific as MS is, you can still have unanticipated interference. Try solvents, including water from a different source. I suspect the change in the baseline is probably due to contamination or composition of mobile phase (as B increases, baseline increases, for example) rather than electronic problems.

Thank you so much, Michele. It really was the water.

We normally stored MilliQ water that was in a different lab in our 20 L container in our lab. The ghost peaks were gone when we used freshly collected water. We were confused by one of the ghost peaks having the same m/z ratio as one of our drug. It was a nice peak and really looked like our drug peak.

Thank you again for your expert advice. We are very grateful to you.