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_d) of metal complexes of deferasirox (DFX, H₃L), a drug used to treat iron overload. Inert Co^IIIL₂³⁻ did not dissociate. The estimated k_d value for Fe^IIIL₂³⁻ was (2.7 ± 0.3) × 10⁻⁴ s⁻¹ (298 K, pH 7.4). The k_d values of other complexes (Al^IIIL₂³⁻, Ni^IIL₂⁴⁻, and Mn^IIL⁻) were in the range 10⁻³–10⁻⁴ s⁻¹. In contrast, Zn^IIL⁻ and Cu^IIL⁻ were too labile to allow k_d estimation. The fact that the half-life of Fe^IIIL₂³⁻ (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 Fe^IIIL₂³⁻. The possibility of a safer iron-chelation therapy that avoids excretion of other essential metal ions such as Zn^II is discussed, highlighting the importance of selectivity in terms of kinetic stability.