I've been using using a nanoACQUITY UPLC system coupled to Synapt G2-S high-definition mass spectrometer operating in positive electron spray ion mode and equipped with hybrid quadrupole time of flight (qTOF) analyser. The following MS conditions used to gave me a good results;

- The 80 °C ion source block temperature capillary voltage = 3 kV, scanning time =0.5 sec, sample cone voltage and source offset = 30 V, nanoflow gas at 0.3 Bar, purge gas at 20 Lh-1 and cone gas flow at 20 Lh-1.

-Data independent acquisition (DIA) method by MSE multiplex mode was used for samples acquisition at T-wave collision-induced dissociation cell filled with argon gas.

and here is the nLC method I am following:

- a nanoEase M/Z BEH C18 (1.7 μm, 130 Å, 75 μm × 100 mm, Waters Corp., USA) at 40 °C and nanoEase M/Z Symmetry C18 Trap Column (100 Å, 5 µm, 180 µm x 20mm, Waters Corp., USA). Milli-Q water and acetonitrile containing 0.1% formic acid were used as mobile phase A and B, respectively, with 1 µL injection volume at 0.3 mLmin-1 flow rate throughout 50 min gradient. Samples were injected into the trapping column at 5 μLmin-1 at 99% mobile phase A for 3 min before being eluted on the analytical column. An initial 1% of mobile phase B and ramped to 85% B over 50 min with the following gradient: 10% B at 2 min, 40% B at 40 min and 85% B at 42 min.

Hopefully that help!

Clean up step might be a concern as well.