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.