Chromatography Forum

Dear all

I have to do an inter-lab-validation where the target analyte has M/Z = 146. Unfortunately I have very high interference with peaks at m/z 145 and 157, which seems to be [2ACN+Cu]+. 146 itself is problematic because it is also [3ACN+Na]+.
Resulting from that my baseline is so high that I can hardly see the analyte at 5 µg/L in clean solvent. But I need <2 µg/L in matrix (liver and milk).
The instrument is a Xevo-TQS, freshly cleaned and in best state (PQ was OK).
I already tried to increase cone cas, increase desolvation temperature, but this did not help much.
I cannot do the most obvious thing: replacing acetonitrile with methanol because the method is already validated. Any other ideas?

Thanks a lot
Jörg

PS: Thanks a lot to the person who put this document online: Common Mass Spectrometry Contaminants and their Sources!

Are you trying to see it in SIR mode? In a triple quad, the interference on the m/z coming out of the source is expected to disappear once using a selective MRM method

Hi Carlo

My measurements are in MRM mode, but the baseline is very high with 5E4 to 5E5 counts for three daughter ions. Usually I stay below 1E4, so I blame it on the crosstalk from the mass peaks close to my analyte.

Regards,
Jörg

Dear all

I have to do an inter-lab-validation where the target analyte has M/Z = 146. Unfortunately I have very high interference with peaks at m/z 145 and 157, which seems to be [2ACN+Cu]+. 146 itself is problematic because it is also [3ACN+Na]+.

Dear Jörg,

is TFA used in your mobile phase?

Are you sure that it is really Cu? Cupper providas a charastic isotopic pattern. I had once problems with a cupper contamination. Problem was a old (~2 years) outer sprayer/probe needle for the sheath gas.

Kind regards
Klaus

Hello Klaus

The instrument has not seen any TFA before (about 1 year old). The isotopic pattern matches to Cu: 145 is about two times the height of 147.

Regards
Jörg

Depending on the probe/source design, the intensity of cluster ions can sometimes be manipulated by varying the ionization voltage & source tuning parameters .

JMB

A second thought is to dope your mobile phase at very low levels with EDTA (or other) to chelate the Cu.
I was going to suggest doping with an inorganic salt to displace the Cu; KCl would shift the m/z 146 to higher value and might even disrupt the MeCN/Cu complex, but would very likely give you [M+K] which is notoriously difficult to fragment by MS/MS.
JMB

A phosphoric acid wash normally cleans the HPLC of all the excess metal which bleeds in the mobile phase.

DO IT ONLY IF YOU KNOW WHAT YOU ARE DOING!

First, all lines (solvents, needle wash, etc) are primed with water.
Disconnecting the dector, MS, column, etc... one purges the system with phosphoric acid HPLC grade 30 % for 30 minutes. The acid must not enter the seal wash lines!. Then all lines are purged with water for at least 4 hours. Make sure that all acid is rinsed by controlling the pH of the water coming out of the system with some litmus paper.

Thanks Carlo

I will keep this in the back of my head as last thing to try. I have played a little more with source settings and I hope that I come to sufficient sensitivity now.
(Moved the needle further away from the cone, increased temperature, decreased spray and increased cone gas).

Regards
Jörg

Remove your metal sinkers from the bottels as well, before performing the wash!

Dear Jörg,

I’m not sure that playing with temperatures or gas-flows will be very helpful in your case. A contamination with cupper is very uncommon and therefore not a problem of the tuning parameters.

If you cannot provide a meaningful reason for this (e.g. cupper containing mobile phase was used before), the origin of the cupper-contamination will be in the metallic parts of your system.

I don’t know the source/probe of your Xevo-TQS in detail, but maybe there are some metal parts soldered together. Over the time the soldered junction will give off some cupper. Also when this parts are not in contact with liquid.

This is almost impossible to observe in a visual inspection (even with microscope) of your probe.

Regards
Klaus