Method translation / LC-MS to LC-QTOF

Hello everyone,
I have a strange problem with the determination of two analytes.
I have a method on LC-MS/MS (MRM), 30 analytes - photoinitiators, which I transfer to QTOF.
All analytes, after small optimizations look excellent.
Scope of the method: 10 - 200 ng/mL
Mobile phase: A: pH=4 , ammonium formate / B: acetonitrile

I have a problem with two:
1-Hydroxycyclohexyl phenyl ketone CAS: 947-19-3

2-Hydroxy-2-methylpropiophenone CAS: 7473-98-5

These two analytes (unproblematically) are determinable by LC-MS/MS technique. I think I could even reduce the LOQ.
However, I do not see them using QTOF. What I would do, they only appear in the range of about 500 ng/mL - I don't understand why. Their monoisotopic mass is neither smaller nor larger than the others.

after creating a PCDL library, I search the analytes using the ALL IONS method (0,20,40 eV).
I have already tried with other eV, lower fragmentation energy, tried to create pseudo-MRM (Target MS/MS method).

I am out of ideas.
LC-QQQ: Agilent 6460 (AJS ESI)
LC-QTOF: Agilent 6546 (Dual AJS ESI)*

Both methods have the same source settings.
Gas Temp: 350
Drying gas: 8 l/min
Nebulizer: 55 psi
Sheath Gas Temp: 400
Sheath Gas Flow: 12 l/min
VCap 4500 V
Nozzle Volatge 300 V
Fragmentor: 60 (also I tried higher)
*Skimmer: 65
* Oct1 RF Vpp 750

  • Hi,

    You have explained your problem very well, how much have you tried the fragmentor voltage value?   Have you gone up to 350?Please try  to increasing by 100. And also try to nozzle voltage and vcap value. How about your signal quality on QQQ. You can also increase your threshold values to 100 on your qtof metod tab.. If the signal is low, you may be eliminated due to threshold.

  • Hi, thank you for your advice. 

    The fragmentation energy for these two compounds is between 55-65 V (QQQ method) . It is relatively lower compared to my other compounds.

    However, during my research I checked the energy between 55 - 145 V (145 V is the value for all the other compounds, using the QTOF technique). I did not try higher values.

    You propose to go as high as 350 V, it sounds to me as high as an abstract value :) I do not have that much experience with QTOF. Does it actually happen that such small molecules sometimes require higher fragmentation energy compared to QQQ?

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