Chromatography Forum

Hello

We have a Waters UPLC/TQ tandem MS and I am losing sensitivity. Area counts of my internal standard is half what I started with (4 months ago).

The system is 6 months old. I've been working with this procedure for about 4 months. In all about 50 runs of 6 to 10 injections. Not that much in my opinion.

The method is for Pentobarbital using ph10 5 mM Ammonium Acetate and ACN (30:70). Negative ESI.

Sample is serum after doing a protein crash with ACN and ZnSO4 (0.1N).

Cleaning the sample cone gives no significant improvement.

So now I'm thinking it's the ESI probe or the ion block.

What would be the most likely culprit? I have little to no experience with this technology and have no experience cleaning the ion block or relacing the capillary and I rather not do any more than I have to. Neither one seems an easy task.

TIA
Mike

Have the area counts of your analyte fallen by about half of what you started with 4 months ago? If both the analyte and IS have decreased over time, I would venture to guess you need to clean the source. You say you have cleaned the cone already. How did you clean it?

Since you are running samples from a crash and shoot method, I am not surprised that the source may need cleaning after 300-500 samples, even though you don't want to have to clean it that often.

It seems unlikely ot be the probe - these either block completely or are fine. If you get a steady spray the probe is probably OK. (take the probe out and run sample through it onto a flat surface you should see the spray as it lands, if its sputtery then replace capillary)

Removing the ion block isn't that complicated. The instructions in the user manual should be fairly detailed. Its only a few allan bolts. It could be that the front hexapole also needs cleaning while you have the ion block off. Again follow the instructions in the manual!

Or you could pay Waters to have one their engineers show you how to do it. You are still in Warrenty? so you might get it for free!

Thanks for the replies.

Guess I'll plan on cleaning the block. Been shown once but it was a long time ago.

Maybe I'll buy an extra ion block since the management insists on PPT extractions.

Mike