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I have been having persistent issues with retention time (RT) shifts on my LC for the past several months, and would appreciate any troubleshooting advice. Each time we turn on the instrument, retention times shift (usually later each time). Usually they are stable within a run, but not always. The change between runs is not usually large but it has added up over time to be quite significant- our database RTs and methods with targeted acquisition windows have all needed to be changed multiple times. The pressure has not changed. We are seeing the same pattern across methods for different analytes that use different columns and mobile phases. We have tried replacing all of the mobile phases. The same thing has been happening on new and old columns. We had preventative maintenance done where they replaced the pump seals, checked that the pumps hold pressure, etc., which bumped the RTs earlier some, but did not help the consistency problems. A Thermo tech spent some additional time testing the instrument to check the flow rate and solvent gradient and found no issues. Their conclusion is that our problems are application based, but our most common methods have run for years and have not had this issue before. Also, we are having the same problem across multiple applications.
More recently, we have swapped out the whole LC pump with one from a different instrument, which again, bumped RTs earlier but didn’t stay stable. It is possible that this pump has the same problem (same model, both are old, and both had significant down time last year). The one we swapped in had not been used in a few months, and its former primary user changed jobs last year so we don’t know if it was running well when it was last being used (or the problem is not the pumps). This week, we swapped the rest of the LC stack, but have not run enough to determine if that worked yet.
What else would you try? We have had projects on hold for months at this point. For targeted things, we can get away with running extra check standards to follow RT shifts, but our NTA work is stuck because of this!
Thank you!
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