Chromatography Forum

Hi all, Im quite new to LCMS and was wondering if anybody else has experineced this/ had any tips.

I've been running standard solutions of my analytes using deuterated internal standards and the internal standard repsonse drops off significantly as analyte concentration increases.

Any ideas on how to fix this??

Thanks

Stephen

Hi Stephen,

This is not uncommon: just ion suppression on your deuterated standard. If you need these highly concentrated standard solutions, there is nothing you can do to avoid this.

But the good news is that it should not be a problem for your quantification: for identical concentrations, the IS response in "real" samples will be as much affected as that in the calibration solution.

Best,
Gaetan

Hi Stephen,

This is not uncommon: just ion suppression on your deuterated standard. If you need these highly concentrated standard solutions, there is nothing you can do to avoid this.

But the good news is that it should not be a problem for your quantification: for identical concentrations, the IS response in "real" samples will be as much affected as that in the calibration solution.

Best,
Gaetan

I would phrase that as "the IS response in 'real' samples SHOULD be as much affected as that in the calibration solution."

You don't know until you test it out and validate it.

Is there any chance you could decrease the concentration of the internal standard as to eliminate the co-eluting suppression??

Indeed, I was too fast: it SHOULD be as much affected. The only way to confirm it is to validate the method.

You may want to increase the concentration of the IS to avoid a too low response at high concentrations of the analyte.

If you have an APCI probe, you could give it a try: APCI is generally less prone to ion suppression. However, sensitivity for polar compounds is usually lower.