The role of N-acetyl-methioninate as a new stabilizer for albumin products.
Sodium octanoate (Oct) and N-acetyl-l-tryptophanate (N-AcTrp) are widely used as stabilizers during the pasteurization of albumin products. However, N-AcTrp has a possible side effect of intracerebral disease. To provide safe and risk-free albumin products, we validated N-acetyl-methioninate (N-AcMet) as a new stabilizer for albumin products. The effect of N-AcMet on oxidation was examined using 2,2'-azobis(2-amidino-propane) dihydrochloride (AAPH) as an oxidizing agent. Carbonyl content in the presence of N-AcMet, as well as that in the presence of N-AcTrp after 24h (Anraku et al., 2004), was significantly decreased. The effect of AAPH on the oxidative status of 34-Cys on human serum albumin was also studied by HPLC. It was found that N-AcMet as well as N-AcTrp, has a large protective effect on the sulfhydryl group after 1h. Further, N-AcMet was found to be a superior radical scavenger to N-AcTrp using 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radicals. The thermal stabilizing role of N-AcMet manifested as an increase in denaturation temperature and calorimetric enthalpy, as determined by differential scanning calorimetry (DSC). In the present study, we suggest that use of N-AcMet in albumin preparation is safe and free of risk of side effects.
Anraku
Makoto
M
Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
Kouno
Yousuke
Y
Kai
Toshiya
T
Tsurusaki
Yasufumi
Y
Yamasaki
Keishi
K
Otagiri
Masaki
M
D004355:Drug Stability; D006801:Humans; D008024:Ligands; D008715:Methionine / Q000031:analogs & derivatives* / Q000502:physiology; D010084:Oxidation-Reduction; D012709:Serum Albumin / Q000378:metabolism*
D008024:Ligands; D012709:Serum Albumin; C006379:N-acetylmethionine; D008715:Methionine