title: Stability of interleukin 1 beta (IL-1 beta) in aqueous solution: analytical methods, kinetics, products, and solution formulation implications.
abstract: The thermal stability of IL-1 beta in aqueous solution as a function of temperature (5-60 degrees C), pH (2-9), buffer (acetate, citrate, tris, and phosphate), and cyroprotectants (sugars, HSA) was investigated in this study. The analytical methodologies included RP-HPLC, SEC, ELISA, IEF-PAGE, SDS-PAGE, and bioassay. The degradation and inactivation of IL-1 beta at or above 39 degrees C were attributed to autoxidation of the two cysteine residues in the denatured protein, followed by hydrophobic/covalent aggregation and precipitation. At or below 30 degrees C, IEF- and SDS-PAGE results suggest a possible deamidation reaction. The difference in mechanism of degradation precludes the prediction of formulation shelf life from accelerated temperature data. Nonetheless, the good stability observed at 5 degrees C suggests that a solution formulation may be feasible for IL-1 beta.
authors.affiliation: Institute of Pharmaceutical Sciences, Syntex Research, Palo Alto, California 94034.
authors.forename: L C
authors.initials: LC
authors.lastname: Gu
authors.forename: E A
authors.initials: EA
authors.lastname: Erdös
authors.forename: H S
authors.initials: HS
authors.lastname: Chiang
authors.forename: T
authors.initials: T
authors.lastname: Calderwood
authors.forename: K
authors.initials: K
authors.lastname: Tsai
authors.forename: G C
authors.initials: GC
authors.lastname: Visor
authors.forename: J
authors.initials: J
authors.lastname: Duffy
authors.forename: W C
authors.initials: WC
authors.lastname: Hsu
authors.forename: L C
authors.initials: LC
authors.lastname: Foster
mesh_terms: D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007375:Interleukin-1 / Q000032:analysis / Q000737:chemistry*; D007700:Kinetics; D012996:Solutions; D013696:Temperature; D014867:Water
chemical_list: D007375:Interleukin-1; D012996:Solutions; D014867:Water