盐酸哌仑西平在水溶液中的降解动力学

Degradation Kinetics of Pirenzepine Hydrochloride in Aqueous Solution

目的:研究盐酸哌仑西平(pirenzepinehydrochloride,PRZ)在水溶液中的降解动力学。方法:采用经典恒温法进行试验,通过高效液相色谱法(HPLC法)检测PRZ的浓度。结果:PRZ在水溶液中的水解为伪一级动力学反应,同时受H+和OH-催化,酸催化速率常数(K1)为0.595h-1·mol-1·L,碱催化速率常数(K2)为4.67×103h-1·mol-1·L,K2是K1的7849倍,表明PRZ在水溶液中主要受OH-催化水解。PRZ在水溶液中的最稳定pH(pHm)为5.1。PRZ在pH1.1、pH5.1、pH7.0和pH10.0(I=0.3)的水解反应活化能(Ea)分别是72.83、105.10、74.33和71.67(KJ/mol),在室温(25℃)下的有效期(t0.9)分别为13.1,783.6,58.2和0.7d;在pH1.1的水溶液中PRZ表观水解速率常数随离子强度(I)的增加而增大;相反,在pH7.9的水溶液中,PRZ表观水解速率常数随离子强度增加而降低。结论:PRZ在强酸和强碱条件下均不稳定,若制成液体制剂可调pH为5.1左右。

AIM:To study the degradation kinetics of pirenzepine hydrochloride (PRZ) in aqueous solution.METHODS:HPLC and classical constant temperature method were used.RESULTS:Hydrolysis rates of PRZ in aqueous solution was found to follow pseudo first-order kinetics.The specific hydrogen catalytic rate constant(K_1) at 85 ℃ was 0.595 h^(-1)·mol^(-1)·L and the specific base catalytic rate constant (K_2) at 85 ℃ was 4.67×10^(3) h^(-1)·mol^(-1)·L,7 849 times greater than K_1.The pH_m for PRZ was 5.1.Activation energies (E_a) of the hydrolysis reaction at pH 1.1,pH 5.1,pH 7.0 and pH 10.0 (I= 0.3) were 72.83,105.10,74.33 and 71.67 KJ/mol, respectively.The shelf lives of PRZ at pH 1.1,pH 5.1,pH 7.0 and pH 10.0 were 13.1,783.6,58.2 and 0.7 days,respectively.A positive effect of ionic strength on rate constant was observed at pH 1.1 and negative effect of ionic strength on rate constant was observed at pH 7.9.CONCLUSION:PRZ is not stable in either acute acid or acute base condition.The pH of the liquid preparation of PRZ should be adjusted to about 5.1.