Chromatography Forum

I've got following settings in LC-MS:

A: Water, 0.1 % FA
B: ACN, 0.1 % FA
total flow: 0.5 mL/min

drying gas: 5L/min
nebulising gas: 1L/min
Heat block temp: 250 C

during the initial minutes of gradients, when A phase dominates, I can observe water droplets in the source window: on the window itself, on the sampling cone, near drying gas outlet port and DL, as well as on the cone from which the needle comes out. Is it ok? If not, how to prevent it?

Could it be responsible for the strange signal I sometimes receive, mostly when A prevails?

Yes, you might be right. I have no idea what instrument you are using, but from the instruments I've used, this seems a bit of a low drying gas flow and low temperature to get rid of 0.5mL/min aqueous solvent. Organic solvents are, of course, easier to dry off.

If you are using something like a single quadrupole instrument, then any droplet that is inadequately dried can enter the mass spec. Not so many droplets will make it all the way to the detector, but some might. The time they arrive at the detector is almost random. The quads are scanning, so depending on the time of arrival, the instrument will look at where the quads have reached in their scan, and assign a mass to the randomly-arriving blob. The symptom is typically a noisy spectrum with the apparent mass of the noise peaks varying from spectrum to spectrum. Typically there will be a big peak in one spectrum, and nothing (or a completely different mass) in the next. This is easiest to see by stepping through individual spectra in an unsmoothed chromatogram. Averaged spectra will contain several random peaks and often look more "real" than they are.

I'd suggest checking the help-files of your instrument to find out if the manufacturers have a recommended set of spray-chamber parameters for your chosen flow. If your drying gas and temperature are much lower than the instrument's maximum values, try increasing them. If necessary, consider putting a tee before the mass spec, and diverting some of the flow to waste, so the instrument doesn't have to handle the whole 0.5mL. Many instruments work very well with 200-300uL/min, and the tee does not reduce sensitivity because ESI gives a signal proportional to concentration, not to amount of material.

Things that needs to taken into consideration:
1. I think 250C was too low temp to vaporize the organic mobile phase and you need to optimize your drying gas @ water droplets formation. I would recommend to perform/Optimize your source/gas parameters.
2. Did you observe the strange noise peak even in blank sample. If yes, then there is contamination in your source module. I would recommend for steam cleaning of the source.

Good luck!

Thanks,
VDN

Your drying temperature is mighty low for LC-MS. I'd start at 300 minimum.

Your flow rate is either too low for a 4.6 mm column or too high for a 2.1 mm column. If you're using a 2.1 mm column you should drop your flow back to something closer to optimum. Your desolvation depends on the source temp, the gas flow rate and temp and the column effluent flow.

Strange noise could easily come from entrained droplets.