An LC/MS/MS question

[Shannon78]

Hi everyone,
I'm using a ThermoFinnigan quadrupole mass spectrometer to quantitate analyte in plasma sample, my trouble is the response of internal standard is instable (ranging from 12000 to 4000) when a same sample is injected, and the response of my analyte is stable. It has been tested that the decomposition of my internal standard will never happen under my equipment conditions. What’s troble with my MS system?
Any reply is welcome!
Thanks.

[Uwe Neue]

Could be matrix interference!

[Shannon78]

Uwe Neue, Thank you for your reply, I agree with you, since the tR is rather short, the matrix effect could exist.

[Jim Shen]

Try this, repeatly inject an unextracted (neat) sample from the same vial. If you get consistent response then you have a matrix suppression issue. If not your mass spec condition is not optimal. In that case test different pHs and mobile phase combinations. Also, you maybe on the wrong interface. If you put something too polar on an APCI you may get unstable response. Verse versa, if you put something too hydrophobic on ESI you may get unstable ionization.

[Shannon78]

Thanks for your help. I learn a lot from ask.