MS ESI ionization of methoxybenzenes in normal phase LC-MS

[phenylbonded]

Hi all,

I am running in some great trouble to see the [M+H]+ peak on positive ESI mode. I am analysing methoxybenzenes like 1,3-dimethoxybenzene (138.07 m/z) . The LC-MS is a normal phase system where THF is used as eluent.

Two main problem arise;
1) Even when infusing directly the 1,3-dimethoxybenzene in methanol in the MS, I get an unknown peak (+304 m/z) that I can not correlate to any adduct.
2) The system should run on tetrahydrofuran (1 mL/min) and methanol (0.5 mL/min) is added just before the MS, to improve ionisation. Unfortunately, THF gives very poor ionisation, to the point no increase in the TIC signal is detected when 1,3-dimethoxybenzene is injected in the system (using a bypass column). The peak is well visible in the UV, but no signal results in MS.

I really need to find reliable parameters to have at least some signal for an adduct I can find with all my methoxybenzenes. At some point I observed the peak [M+Na]+ but it is no longer the case for some reason.
I tried to change the ionisation solvent (0.5 mL/min) to the following solvent list, but nothing worked:
MeOH
MeCN
0.1% HCOOH MeOH
0.1% HCOOH MeCN
10 mmol/L NH4HCOO in MeOH
1 mmol/L NH4HCOO in MeCN
1 mmol/L AgNO3 in MeOH
1 mmol/L AcONa in MeOH

What to do now? It seems that most often people see at least some [M+H]+ peak, but in my case it is non existent... What to optimise or try first?
Do not hesitate if you need any more info!

I used the following parameters:
cone voltage: 4.5 kV
dessolvation line voltage: 0V
heat block temperature: 400°C
dessolvation line temperature: 250°C

[Gaetan Glauser]

Hi,

I have no experience with these particular molecules, but I would intuitively be tempted to favour APCI over ESI, and RP-LC over NP-LC. Is it something you could consider testing or are you stuck with this set up? Also, if you have a GC-MS in the lab, that may be worth a try.

[phenylbonded]

As a follow up on my question, I could manage to obtain some ionization with isopropanol as ionization solvent. Although it is not so reliable. Indeed a reverse phase system would be much better for MS signal but in my case it is not possible...