Nickerson B, Cunningham B, Scypinski S
Analytical Research and Development, Hoffmann-La Roche Inc., Nutley, NJ 07110-1199, USA.
J Pharm Biomed Anal. 1995 Dec;14(1-2):73-83. doi: 10.1016/0731-7085(95)01612-0.
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.
Ro 23-9424是一种广谱抗菌剂，由头孢菌素和喹诺酮部分通过酯键连接而成。该化合物在水中的溶解度有限，但在碱性pH值下更易溶解。然而，如此高的pH值会由于酯键的不稳定性而导致稳定性问题，并导致游离喹诺酮和头孢菌素部分的形成。溶解度和稳定性之间的平衡给该化合物的制剂开发带来了挑战。因此，在不同溶剂系统中复溶后，有效监测Ro 23-9424的稳定性非常重要。通过这种方式，可以确定一种不会导致药物降解的稀释剂。开发并验证了一种毛细管电泳方法来监测Ro 23-9424的稳定性。该方法被发现符合方法精密度、系统精密度、线性以及检测限和定量限的可接受标准。该方法用于监测Ro 23-9424在水中以及在旨在模拟药物递送系统的L-精氨酸-苯甲酸钠-盐稀释剂中的稳定性并测量其半衰期。这项工作表明，毛细管电泳可用于比较药物在不同溶液中的稳定性，以辅助制剂开发。
