THE USE OF CAPILLARY ELECTROPHORESIS TO MONITOR THE STABILITY OF A DUAL-ACTION CEPHALOSPORIN IN SOLUTION

Ro 23-9424 is a broad-spectrum antibacterial agent consisting of a cep halosporin and a quinolone moiety which are held together by an ester linkage. This compound has limited solubility in water but is more sol uble at alkaline pH. Such high pH values, however, lead to stability p roblems due to the lability of the ester linkage, and result in the fo rmation of the free quinolone and cephalosporin moieties. The balance between solubility and stability presents a challenge in formulation d evelopment for this compound. Thus, it is important to effectively mon itor the stability of Ro 23-9424 after it has been reconstituted in di fferent solvent systems. In this manner, a diluent which does not lead to degradation of the drug can be identified. A capillary electrophor esis 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 qua ntitation. The method was used to monitor the stability and measure th e half-life of Ro 23-9424 in water and in an L-arginine-sodium benzoat e-saline diluent designed to mimic the drug delivery system. This work shows that capillary electrophoresis can be used to compare the stabi lity of a drug in different solutions as an aid in formulation develop ment.