title: Stability of an anti-stroke peptide: driving forces and kinetics in chemical degradation.
abstract: NR2B9c (Lys-Leu-Ser-Ser-Ile-Glu-Ser-Asp-Val) is a 9-amino acid peptide that has been illustrated to be a potential anti-stroke drug. For more effective treatment, suitable drug delivery systems should be developed. However, little is known about the stability of NR2B9c which is essential to its formulation. In this study, a reversed-phase high-performance liquid chromatography (HPLC) was applied to study the forced degradation behavior and stability of NR2B9c. HPLC studies were performed with an C8 column using a mobile phase consisting of acetonitrile (14.5:85.5, v/v) and aqueous solution (0.1% trifluoroacetic acid (TFA) and 0.05 M KH2PO4). The flow rate and the wavelength set during HPLC detection were 1.0 mL/min and 205 nm, respectively. The degradation pattern of NR2B9c aqueous solution followed pseudo first-order kinetics. The degradation rate at pH 7.5 was the slowest according to the plotting V-shaped pH-rate profile. The influence of temperature on the rate of reactions was interpreted in terms of Arrhenius equation (r(2)>0.98). Thermodynamic parameters were calculated based on Eyring equation (r(2)>0.98). The concentrations of drug, buffer species, buffer concentrations, oxidation and organic solvents have noticeable effects on the degradation of NR2B9c while ultrasound shows little impact under the experimental conditions. In a word, this study may give a detailed description of stability of NR2B9c.
authors.affiliation: School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, People's Republic of China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: School of Pharmacy, China Pharmaceutical University, Nanjing 210009, People's Republic of China.
authors.forename: Fengzhen
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: The Second People's Hospital of Changzhou, Affiliated Hospital of Nanjing Medical University, Xinglong lane No. 48, Wuxi 214000, People's Republic of China.
authors.forename: Shuning
authors.initials: S
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wu
authors.affiliation: Wuxi Hospital for Maternal and Child Health Care, Affiliated Hospital of Nanjing Medical University, Ash lane No. 48, Wuxi 214000, People's Republic of China.
authors.forename: Sunmin
authors.initials: S
authors.lastname: Jiang
authors.affiliation: School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, People's Republic of China.
authors.forename: Qunwei
authors.initials: Q
authors.lastname: Xu
authors.affiliation: School of Pharmacy, Nanjing Medical University, Hanzhong Road No. 140, Nanjing 210029, People's Republic of China. Electronic address: dyzhu@njmu.edu.cn.
authors.forename: Dongya
authors.initials: D
authors.lastname: Zhu
mesh_terms: D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006861:Hydrogen Peroxide / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000528:radiation effects; D009842:Oligopeptides / Q000737:chemistry* / Q000528:radiation effects; D009994:Osmolar Concentration; D016877:Oxidants / Q000737:chemistry; D010084:Oxidation-Reduction; D013010:Sonication; D020521:Stroke / Q000188:drug therapy; D013696:Temperature
chemical_list: D018696:Neuroprotective Agents; D009842:Oligopeptides; D016877:Oxidants; D006861:Hydrogen Peroxide
keywords: Forced degradation; HPLC; Solution; Stability