Differentiation of flavonoid congeners remains a challenging analytical problem and confirming the structures of the different isomers is difficult, even when they can be adequately separated from mixtures. In the present report, in order to overcome the limits of our recently proposed method that relies on the distinctive CID behaviors of [(flavonoid - H(+)) + Cu(2+)] complexes to obtain direct structural evidences, we decided to investigate the possibility of using Pb(II) complexation to generate significant differences upon CID. We selected five flavonoid diglycosides with targeted structural features to estimate the applicability of this methodology. Electrospray ionization from methanol-not acetonitrile-solutions was advantageously used for preparing the [(flavonoid diglycoside - H(+)) + Pb(2)+](+) complexes. Upon collisional activation, [(flavonoid diglycoside- H(+)) + Pb(2+)](+) ions mainly dissociate by glycosidic bond cleavage. Nevertheless, specific cross-ring cleavages are also induced and lead to a clear-cut determination of (i) the nature of the disaccharide group, i.e. rutinose or neohesperidose, (ii) the nature of the aglycone part, flavanone or flavone and (iii) the relative position of the disaccharide substituent on the aglycone part, i.e. 3-O- vs 7-O positions.