The effect of aggregation inhibitors and antioxidants on the stability of hemin solutions.

Despite their importance as infusions for the treatment of porphyrias, aqueous solutions of hemin can be quite unstable, with a reported half-life of a few hours. We have examined factors which affect the stability of hemin solutions in order to identify possible excipients and conditions which would increase the stability. In agreement with previous reports, we have found that human serum albumin leads to stabilization of hemin solutions; polyvinylpyrrolidone is also an effective stabilizer of hemin. Imidazole, caffeine, and niacinamide were also found to stabilize hemin, apparently by complexing to hemin and preventing the formation of hematin dimers. Addition of certain antioxidants, e.g., butylated hydroxyanisole and N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), led to stabilization of hemin, suggesting that radicals are involved in the degradation process. A comparison was also made by HPLC analysis of the hemin autooxidation products with those from the reaction of hemin with hydrogen peroxide; the results indicate that the products are similar but not identical. The implications of the results for clinical use of hemin solutions are discussed.