Kinetic aspects of iron(III)-chelation therapy with deferasirox (DFX) revealed by the solvolytic dissociation rate of the Fe(III)-DFX complex estimated with capillary electrophoretic reactor.

Capillary electrophoresis was used to estimate the solvolytic dissociation rate (k) of metal complexes of deferasirox (DFX, HL), a drug used to treat iron overload. Inert CoL did not dissociate. The estimated k value for FeL was (2.7 ± 0.3) × 10 s (298 K, pH 7.4). The k values of other complexes (AlL, NiL, and MnL) were in the range 10-10 s. In contrast, ZnL and CuL were too labile to allow k estimation. The fact that the half-life of FeL (43.3 min) is shorter than the blood half-life of DFX (8-16 h) implies that the blood concentration of DFX should be high enough to prevent dissociation of FeL. The possibility of a safer iron-chelation therapy that avoids excretion of other essential metal ions such as Zn is discussed, highlighting the importance of selectivity in terms of kinetic stability.