Ortiz C S, de Bertorello M M
Departamento de Farmacia, Facultad de Ciencias Quimicas, Universidad Nacional de Córdoba A.P. 4, C.C. 61-5000 Córdoba, Argentina.
Talanta. 1998 Aug;46(6):1537-45. doi: 10.1016/s0039-9140(98)00046-0.
The goal of this study was to determine the kinetic parameters involved in the decomposition of 2-(5-methyl-4-isoxazolylamino)-N-(5-methyl-4-isoxazolyl)-1,4-naphthoquinone-4-imine (1) in aqueous solution and to identify the main degradation products. An isocratic HPLC assay was used to study the degradation rate of 1. The products of hydrolysis were identified by comparison of their retention times with those of authentic samples. The amount of 1 and the two degradation products resulting from storage of 1 in various buffer solutions was followed in function of time by a reversed-phase HPLC stability-indicating method. The observed degradation rates followed pseudo-first-order kinetics at constant pH, temperature and ionic strength. The logk-pH-profile was constructed at 35 degrees C from the first-order rate constants obtained from studies at pH values ranging from 0.88 to 10.80 (mu=0.5 M). Hydrolysis in the acidic and alkaline media resulted in the formation of two degradation products in each case. The pH-rate profile of 1 in buffer solution was adequately described using a four-term rate equation. The obtained pH-rate profile indicated specific acid-base catalysis with a region of maximum stability between pH 6.40 and 7.40 which can be adequate for formulations of 1.
本研究的目的是确定2-(5-甲基-4-异恶唑基氨基)-N-(5-甲基-4-异恶唑基)-1,4-萘醌-4-亚胺(1)在水溶液中分解所涉及的动力学参数，并鉴定主要降解产物。采用等度高效液相色谱法测定1的降解速率。通过将水解产物的保留时间与标准样品的保留时间进行比较来鉴定水解产物。采用反相高效液相色谱稳定性指示方法，跟踪1在各种缓冲溶液中储存时1及其两种降解产物的量随时间的变化。在恒定的pH、温度和离子强度下，观察到的降解速率符合准一级动力学。根据在pH值范围为0.88至10.80(μ = 0.5 M)的研究中获得的一级速率常数，在35℃下构建logk-pH曲线。在酸性和碱性介质中的水解在每种情况下都产生两种降解产物。使用四项速率方程充分描述了1在缓冲溶液中的pH-速率曲线。所获得的pH-速率曲线表明存在特定的酸碱催化作用，在pH 6.40至7.40之间存在最大稳定区域，这对于1的制剂可能是合适的。
