The role of N-acetyl-methioninate as a new stabilizer for albumin products

• Published in: International journal of pharmaceutics Vol. 329; no. 1; pp. 19 - 24
• Main Authors: Anraku, Makoto, Kouno, Yousuke, Kai, Toshiya, Tsurusaki, Yasufumi, Yamasaki, Keishi, Otagiri, Masaki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.02.2007; Elsevier
• Subjects: Albumin; Antioxidant activity; Biological and medical sciences; Calorimetry (DSC); Drug Stability; General pharmacology; Humans; Ligands; Medical sciences; Methionine - analogs & derivatives; Methionine - physiology; N-Acetyl- l-methioninate; Oxidation; Oxidation-Reduction; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Serum Albumin - metabolism; Sulfhydryl groups; Albumin; Oxidation; Sulfhydryl groups; N-Acetyl- l-methioninate; Calorimetry (DSC); Antioxidant activity; Differential scanning calorimetry; Pharmaceutical technology; N-Acetyl-L-methioninate; Metabolism; Pharmacokinetics; Antioxidant
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2006.08.014

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 24 h ( 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 1 h. 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.