I have a problem with my LCMS. I developed a method ca. 3 month ago and now that I have to validate it, I have a problem with tailing in MS. I did several test changing all I could change: the connector to the nebulizer of the MS, cleaned the MS,by-passed the switch valve waste-MS, prepared freshly solutions and eluents, test all the fittings of the instrument, tested 4 different columns, autotuned the MS and the problem still doesn't seems to solve.
I run the same method on our Q-TOF in scan mode and the peak looks ok. also in the triple quad scan is ok but SIM and MRM I have tailing.
What could be the reason? what I can try next?