title: The use of capillary electrophoresis to monitor the stability of a dual-action cephalosporin in solution.
abstract: Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cephalosporin and a quinolone moiety which are held together by an ester linkage. This compound has limited solubility in water but is more soluble at alkaline pH. Such high pH values, however, lead to stability problems due to the lability of the ester linkage, and result in the formation of the free quinolone and cephalosporin moieties. The balance between solubility and stability presents a challenge in formulation development for this compound. Thus, it is important to effectively monitor the stability of Ro 23-9424 after it has been reconstituted in different solvent systems. In this manner, a diluent which does not lead to degradation of the drug can be identified. A capillary electrophoresis method was developed and validated to monitor the stability of Ro 23-9424. The method was found to meet acceptable criteria for method precision, system precision, linearity and limits of detection and quantitation. The method was used to monitor the stability and measure the half-life of Ro 23-9424 in water and in an L-arginine-sodium benzoate-saline diluent designed to mimic the drug delivery system. This work shows that capillary electrophoresis can be used to compare the stability of a drug in different solutions as an aid in formulation development.
authors.affiliation: Analytical Research and Development, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199, USA.
authors.forename: B
authors.initials: B
authors.lastname: Nickerson
authors.forename: B
authors.initials: B
authors.lastname: Cunningham
authors.forename: S
authors.initials: S
authors.lastname: Scypinski
mesh_terms: D000890:Anti-Infective Agents; D002439:Cefotaxime / Q000031:analogs & derivatives* / Q000032:analysis; D002511:Cephalosporins / Q000032:analysis*; D004355:Drug Stability; D019075:Electrophoresis, Capillary; D016576:Fleroxacin / Q000031:analogs & derivatives* / Q000032:analysis; D024841:Fluoroquinolones; D006207:Half-Life; D007700:Kinetics; D012996:Solutions; D014867:Water
chemical_list: D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D012996:Solutions; D014867:Water; C060441:Ro-23-9424; D002439:Cefotaxime; D016576:Fleroxacin