Analyte stability vs instrument stability

[brinker]

Does anyone have any suggestions on how to differentiate between stability of an analyte, and stability of an LCMS? We have an LCMS method for six structurally very similar compounds, running on an Orbitrap. The matrices are biological fluids or tissues, and even though we do SPE, after a while the peak areas decrease substantially, which usually means it's time for a front end cleaning. We're using deuterated analytes as internal standards, so this decrease hasn't been a problem for our analyses. But now the question of the stability of the analytes has come up. My sense, from working with the standards for a few years now, is that they're pretty stable, but we need to get some numbers for this - and we're thinking of looking at stability over a year or more. The problem is that if I prepare a batch of standards and put them in the freezer, in six months the peak areas may be different just because of how dirty the MS is. I'm not sure that it would be feasible to do a front-end cleaning just before every test batch. Does anyone have a better idea? Is there something that's really, really stable that could be used for comparison?

Thanks very much for any suggestions!

[Gizmo]

Without knowing the nature of the chemicals you are working with and with a caveat that far better suggestions are surely to be found, maybe throwing a little caffeine or sucralose in the mix might be a means to test stability of your items in storage. I believe caffeine can be found as a C13 for internal standard options. Not sure about sucralose for C13 or other modifications but the stability on that is good enough to be used as an indicator of wastewater detection

[James_Ball]

Without knowing the nature of the chemicals you are working with and with a caveat that far better suggestions are surely to be found, maybe throwing a little caffeine or sucralose in the mix might be a means to test stability of your items in storage. I believe caffeine can be found as a C13 for internal standard options. Not sure about sucralose for C13 or other modifications but the stability on that is good enough to be used as an indicator of wastewater detection

That would be a good way to check it.

Also, if every time you do a cleaning the response returns to what you had with the last known clean instrument, then that would point to the instrument causing the problem more than analyte stability. If the analyte was not stable, then even a cleaning would not return the response to normal.