Different options of liquid chromatography-mass spectrometry were used to establish the most suitable ion source and conditions to analyse or detect some low-molecular mass phenols, flavan-3-ols, and apply such conditions to a complex sample (wine). Data presented in this work confirm the great utility of atmospheric pressure-ionisation electrospray mass spectrometry coupled to HPLC for analysis of phenolic compounds, under negative mode in the case of low-molecular mass phenols, and under both positive and negative modes in flavan-3-ol compounds. A fragmentor voltage of 60 V could be the most suitable for analysing the compounds under study.