I am doing DNA encoding, I want to monitor the reactions using LCMS 2020, during first round I got the MS peak (5000), but during second cycle the DNA is big and no quality peak now visible. Wish to resolve this
Knowledge how the machine operates is one issue, but more important are the applied settings. I haven't worked with Shimadzu spectrometers nor did any MS of oligos, but I used MS techniques for peptides and proteins. What I learned is that the skilled person is the most important factor here. So, if I were you, I would find an expert.
Mimicking of how to operate the instrument is insufficient, you need to know how to adjust settings like voltage or neutral gas flow rate, which can entirely change your mass spectrum. And these vastly depend on the instrument, on the ionization type (I assume ESI on your case), also if there's an ion trap or is it TOF, and many other factors. How sensitive your sample is is also crucial, as it may get degraded in the instrument under specific settings and not when you tune some parameters. Also using the pre-installed modes from a company often need some further tuning. The best call is to find an expert on nucleic acids/oligonucleotide mass spectrometry and let him do the experiment (or teach you).