Analytical and Biological Implications of Complex Combinations of Hydroxyurea with Iron (II)

Hydroxyurea (Hy) in aqueous solutions has several tautomeric forms due to the formation of a >N-OH bond. The azometinic group >C=Nis present in all these tautomeric forms. The structural forms influence the hydrophil-lipophil character of Hy and it determines the complexing of the Fe(II) ions, thus explaining the appearance of anemia, due to the treatment with hydroxyurea. The paper presents a spectrophotometric absoption method in UV through which Fe(II) is determined quantitatively using Hy as reagent, as well as the complexing percentage of these ions from the organism following the administration of the medicine. The complex formed by Hy with the Fe(II) ions is stable in water for a pH = 7.4-7.6 with a maximum of absorption at 267nm and molar absorptivity of ε = 3.4559 ·104 ·mol-1·L·cm1. The combination rate has been established using the isomolar series method at 1:1 (M/L). The calculated value of the stability constant is 1.26·106. The LambertBeer law is observed in the concentration interval 10-60 μg Fe(II), in a final volume of 10 mL. The correlation coefficient (r2) is 0.9999, the standard deviation (SD) = 0.0114 (n = 6). The detection limit (LD) is 2.71μg/mL and the quantification limit (LQ) is 9.04 μg/mL. Under these conditions, the complexing reaction of Fe(II) is interfered by the cations of Fe(III), Co(II). The proposed method has been applied successfully in order to determine Fe(II) from pharmaceutical products and the Hy-Fe(II) complex present in the urine of the patients that underwent treatment with Hydreea of 500mg for more than ten years.