low MS response at high organic solvent(?)

[guoyang]

Hi, everybody!
Rencently I do a LC-MS.
LC condition: M.P.: CH3CN: H2O =40:60 0min
100:0 15-30min
flowrate: 1ml/min
The peak at RT=18min give low MS response which hard to check and UV signal is about 200mV. I want to know why MS response is low at high organic solvent? Are there any good method to improve MS response?

[guoyang]

I use Agilent 6120 LC-MS.
And how to set fragmentor voltage for different molecule weight?

[Ron]

If you are using ESI the analytes are ionized in solution, so as high organic concentration reduces ionization as a general rule sensitivity is lower as organic concentration increases. Are you adding any modifier to your mobile phase to enhance ionization?

[Uwe Neue]

I disagree. HILIC (which contains a lot of organic solvent) has been used with advantage and gain in sensitivity over RP separations with high water content (publications by Naidong Weng and others). However, it appears that your analyte is eluting in 100% organic. Under these circumstances you may loose sensitivity. Post-column addition might help, if this is the case.

[jiang295]

is this advantage with HILIC associated with ionization of analyte rather than solvent effect.

I disagree. HILIC (which contains a lot of organic solvent) has been used with advantage and gain in sensitivity over RP separations with high water content (publications by Naidong Weng and others). However, it appears that your analyte is eluting in 100% organic. Under these circumstances you may loose sensitivity. Post-column addition might help, if this is the case.

[guoyang]

If you are using ESI the analytes are ionized in solution, so as high organic concentration reduces ionization as a general rule sensitivity is lower as organic concentration increases. Are you adding any modifier to your mobile phase to enhance ionization?

I didn't add any modifer to mobile phase. Does this will increase ionization by adding modifier? If it is true, what modifier could I use?

[H.Thomas]

A modifier will probably enhance your sensitivity. Try 0.1% formic or acetic acid.

If you get 200 mAU in UV your MS should be overloaded. If you get a low response in MS there is something seriously wrong. Is your instrument tuned and optimized for your analyte?

[lmh]

(1) I'd side with Uwe Neue on the issue of signal strength in organic versus water solvents, but I have no theoretical explanation for Ron, Sorry!
(2) No, the difference between signal strength in HILIC and RP is entirely due to solvent; the MS has no idea what column is upstream, it merely knows what solvent mix is arriving.
(3) For most analytes I'd agree with H. Thomas, but if you are unlucky and are trying to investigate something with very few ionisable groups, you may have a large UV signal and nothing in ESI. Example is anthracene.

[H.Thomas]

@lmh: I did not think about PAHs, sure they will give such an effect. Another example, that some information given by the asker will help...

AFAIK the physical explanation for better response in higher percentage organic is the better desolvation.