*3.6. High-Resolution Mass Spectrometry (HR-MS) Experiments*

HR-MS and HR-MS/MS were performed on a Waters Xevo G2 QTOF mass spectrometer (Waters, Manchester, UK) with ESI in positive mode (ESI+) and in few cases in negative mode (ESI−). For both modes, the instrument parameters were as follows: for MS analysis, cone voltage 30 or 50 V, source temperature 110 ◦C, desolvatation temperature 300 ◦C, cone gas flow rate 20 L h−1, scan range *m*/*z* 50–1200; for MS/MS analysis, three collision energies were used 15, 25 and 35 V with the cone voltage maintained at 30 V or 50 V and the spectra were acquired with a mass precursor ion selection of 3 Da. All analyses were performed using the lockspray, which ensured accuracy and reproducibility. Leucine enkephalin (1 ng μL<sup>−</sup>1) introduced by a lockspray at 3 μL min−<sup>1</sup> was used as the lockmass generating reference ions at *m*/*z* 556.2771 or 554.2615 in positive or negative mode respectively. The MassLynx software was used to calculate the most probable chemical formula and the theoretical exact mass of the molecular and fragment ions by comparison with their measured accurate ionic masses.
