title: Solution stability of the monoclonal antibody-vinca alkaloid conjugate, KS1/4-DAVLB.
abstract: A 3-month solution stability study at 5 degrees C of the monoclonal antibody-vinca alkaloid conjugate KS1/4-DAVLB indicated that phosphate-buffered saline solutions at pH 4.5-5.5 had little tendency to lose vinca by hydrolysis, improved vinca stability, showed acceptable physical stability, and formed minimal amounts of soluble aggregates compared to solutions at pH 6.5-7.4. Hydrolysis and aggregation with concomitant loss of stability were accelerated at 30 degrees C throughout the pH range investigated. As determined by ELISA, the binding properties of KS1/4-DAVLB to tumor antigens were not affected by pH or temperature. A formulation suitable for initial clinical trials in cancer patients is described.
authors.affiliation: Pharmaceutical Product Development Division, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
authors.forename: A
authors.initials: A
authors.lastname: Riggin
authors.forename: D
authors.initials: D
authors.lastname: Clodfelter
authors.forename: A
authors.initials: A
authors.lastname: Maloney
authors.forename: E
authors.initials: E
authors.lastname: Rickard
authors.forename: E
authors.initials: E
authors.lastname: Massey
mesh_terms: D000911:Antibodies, Monoclonal / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D004797:Enzyme-Linked Immunosorbent Assay; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology; D011506:Proteins / Q000032:analysis / Q000737:chemistry; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D014748:Vinca Alkaloids / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D011506:Proteins; D012996:Solutions; D014748:Vinca Alkaloids