A method based on the analysis of trimethylsilyl (TMS) derivatives by capillary gas chromatography electrospray ionization mass spectrometry (GC-ESI/MS) was proposed. To improve separation, analytes were derivatized to their TMS derivative. During ESI analysis, TMS derivatives may hydrolyze back to their polar native form and are thus suitable for ESI analysis. Several types of analytes were studied to investigate the potential of the approach. Not all TMS derivatives hydrolyzed back to their native form as anticipated. Incomplete hydrolysis was observed for TMS-organic acids and TMS-nonchlorinated phenols. For TMS-chlorophenols, the observation of only the [M - H] ion suggested that these phenols were hydrolyzed back to their native form. For TMS-beta agonists, the hydrolysis rate was low; therefore, the hydrolysis product was not detected. Both TMS-chlorophenols and TMS-beta agonists provide a sensitivity in the range of low parts per billion (0.25-5 ng/ml and 0.5-10 ng/ml respectively). Copyright © 2016 John Wiley & Sons, Ltd.