Chromatography Forum

I do not quite understand your question (maybe you could clarify) but theoretically you could use an internal standard that produce molecular ions in both positive and negative ionization modes (i.e. zwitterionic compounds is a good example...).

I mean, Is it valid to have a quantification of a substanse which is been measured in ESI+ by using an internal standard measured in ESI-, (they are well seperated in my current Chromatography conditions). This is because I want to avoid the addition of another compound in my analysis (I have already 3: two analytes ESI+ and ESI- and one internal ESI-)
So In other words is it possible to use the existing internal for the quantitation of both analytes?[quote][/quote]

I see now what you mean...

I would say that in this case you would be able to correct for general drifting of the instrument, however, ion suppression effects might be totally different in positive vs. negative mode and your internal standard won't be able to correct for those...

Your scheme will correct for variabilities between the time of addition of the internal standard and the time of the sample injection. After that, the assumptions of internal standard calibration may no longer hold. The big assumption is that the IS and the analyte behave the same way in the detector. Until you prove that, your method is not validated. In general, you can't assume that the MS source is well behaved, but you can prove it.