The Competitive influence of Li+, Na+, K+, Ag+, and H+ on the fragmentation of a PEGylated polymeric excipient.

The collisionally activated dissociation (CAD) and electron capture dissociation (ECD) of doubly charged tocopheryl polyethylene glycol succinate (TPGS) have been examined. Li(+), Na(+), K(+), Ag(+), and H(+) were selected in the study, and the competitive influence of each ion was investigated by fragmenting TPGS attached with two different cations, [M + X1 + X2](2+) (X1 and X2 refer to Li(+), Na(+), K(+), Ag(+), H(+)). For metallic adducts, CAD results show that the dissociation of ionic adducts from the precursor is most likely depending on the binding strength, where the affinity of each ion to the TPGS is in the order of Ag(+) ≈ Li(+) ˃ Na(+) ˃ K(+). Introducing more strongly bound adducts increases fragmentation. During ECD, however, the silver cation is lost most easily compared with the other alkali metal ions, but silver also shows a dominant role in producing fragmentations. Moreover, the charge carriers are lost in an order (Ag(+) ˃ Na(+) ˃ K(+) ≥ Li(+) where the loss of Ag is most easily) that appears to correlate with the standard reduction potential of the metallic ions (Ag(+) ˃ Na(+) ˃ K(+) ˃ Li(+)). The ECD results suggest that the reduction potential of the charge carrier could be an important factor influencing the fragmentation, where the ion with a high reduction potential is more effective in capturing electrons, but may also be lost easily before leading to any fragmentation. Finally, a proton has the weakest binding with the TPGS according to the CAD results, and its dissociation in ECD follows the order of the reduction potential (Ag(+) ˃ H(+) ˃ Na(+) ˃ K(+) > Li(+)).