Hi, I'm a Mass Spec person who is new to LC. We have an LC-MS (Agilent 1200 with ESI on an Agilent 6230 TOF) on which I tried to run some compounds for an organic chemistry student who needs some high resolution MS for his intermediate compound validation. These intermediates employ either Tertbutyldimethylsilyl (TBS) and/or Triisopropyl silyl (TIPS) groups. The starting compound (no TIPS or TBS) with a m/z 300 shows up well along with one of the TIPS functionalized compounds (m/z 497). However, some of the other compounds with parent mass weight of m/z 385-496 do not show up, though other species appear on Extracted Ion Chromatograms. I would tell the guy that the Mass Spec doesn't lie but the NMR spectra confirm their existence. So possibly getting them ionized may be the issue. What I would like to know is if anyone out there has successfully monitored silyl derived compounds on an LCMS platform as opposed to a GCMS and has any advice.

Currently we are injecting ~1ng (0.2uL from a 5ug/ml solution) with 70/30 ACN/H2O with 0.1% formic isocratic mobile phase on a C18 Eclipse 5um 15mm column with a flow rate of 0.4l/min.