HPLC Rt Help

Hi fellow chempros! I’m a quality control specialist at a facility that produces radio pharmaceuticals. I handle three different HPLC systems at my job. Two are Agilent’s (1260 Infinity and 1260 Infinity II) and one is a ThermoFisher Dionex ICS.

I’ve experienced retention time shifting on all of these instruments, by up to 2-3 minutes. For the Agilent systems, we’ve been transitioning to using multiple solvent bottle wells for mixed mobile phases (like 70/30 MQ/MeOH) instead of manually mixing into a single solvent bottle because there was some concern in the team about human error and inconsistent mobile phase preparation. That seems to have improved retention times consistency somewhat. We’ve also disassembled portions of the instrument to clean, which helped. We have a maintenance contract and get regular servicing on the HPLC’s as well.

The Dionex is older and no longer has a service contract. We’ve seen good consistency in retention times, but today our retention time for a standard shifted from 9.5 min to 11 min for no apparent reason. I prepared the mobile phase and standard per our standard protocol. I can’t see any reason why the retention time suddenly shifted, but the inconsistency affects my ability to collect our daily instrumental suitability data.

I have been in this job for less than a year and it seems that most of these issues have come up since I joined the team. There’s a distinct tone that whatever issues we’ve been having are my fault and due to my own errors or incompetence. That could be true, but I really can’t see anything that I’m specific doing incorrectly or inconsistently that would cause these problems. It’s doing a number on my confidence and I could use some insight or advice from fellow professionals. Thanks!