Small molecule LC-MS troubles

[ManaJane]

Hello,

I am running a Waters UPLC-TQD to quantify three different compounds by MRM. The transitions I am monitoring are 195/105, 145/66, and 127/58. When I first begin running the method, I had okay precision (+/- 10% RSD) and okay accuracy (+/- 15%). I was only able to reach that kind of performance twice. Since that time I have had a number of issues with accuracy and precision. Cleaning the source of the mass spec does help a little. I have also modified the source temps in an effort to remove any interferences. I am still have problems though. I am lucky if I can get +/- 15% rsd for system precision and +/- 30% for accuracy. Does anyone have any suggestions for how I can improve my method or why this may be happening. I am at a loss.

Thanks.

[H.Thomas]

MRM is fine, but the drawback is that it is blind to anything but your target transitions. You might want to run your samples in SCAN-mode to see if there is anything interfering with your peaks. Maybe you'll have to finetune your separation to get rid of interferences.

[kerri]

What happens to your method when you flush your column (with ACN or IPA)?

[Alp]

Are you using internal standards for all three compounds?
If so, do the internal standards "follow the analytes" in terms of recovery and retention time etc.

What sort of ionization process are you using. APCI or ESI?

Alp