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目的:研究酮洛芬-丹皮酚偶合物(Ket-Pae)的稳定性及其降解动力学。方法:RP-HPLC测定Ket-Pae的溶解度和油水分配系数,通过初步稳定性试验考察Ket-Pae稳定性,并进行不同pH条件和血浆中的降解动力学研究。结果:在高温条件下Ket-Pae有明显降解的现象;与酮洛芬和丹皮酚相比,Ket-Pae的水溶性降低200～300倍,lnP上升4倍左右;Ket-Pae的降解曲线呈V-型分布,pH=5时最稳定(t1/2=14.4d)。在血浆中的Ket-Pae降解半衰期很短(t1/2=1.3min),可迅速降解为酮洛芬和丹皮酚。结论:Ket-Pae的脂溶性增强,其稳定性受高温和pH的影响。
Objective: To study the stability and degradation kinetics of ketoprofen-paeonol conjugate (Ket-Pae). Methods: The solubility and oil-water partition coefficient of Ket-Pae were determined by RP-HPLC. The stability of Ket-Pae was investigated by preliminary stability test and the kinetics of degradation was studied under different pH conditions and plasma conditions. Results: Ket-Pae showed obvious degradation under high temperature. Compared with ketoprofen and paeonol, the water solubility of Ket-Pae decreased 200 ~ 300 times and lnP increased about 4 times. The degradation curve of Ket-Pae V-type distribution, the most stable at pH = 5 (t1 / 2 = 14.4d). Ket-Pae has a short half-life in plasma (t1 / 2 = 1.3 min) and rapidly degrades to ketoprofen and paeonol. Conclusion: Ket-Pae liposolubility increased, its stability is affected by high temperature and pH.