Krzek Jan, Kwiecień Anna, Zylewski Marek
Collegium Medicum, Department of Inorganic and Analytical Chemistry, Jagiellonian University, Kraków, Poland.
Pharm Dev Technol. 2006;11(4):409-16. doi: 10.1080/10837450600770106.
The main objective of this research was to investigate the relationship between the polarity of atenolol, acebutolol, and propranolol described by logP and kinetic and thermodynamic parameters characterizing their degradation process in acidic solution. Hydrolysis was carried out in hydrochloric acid at molal concentrations of 0.1 mol/L, 0.5 mol/L, and 1 mol/L for 2 hr at 40 degrees C, 60 degrees C, and 90 degrees C. Chromatographic-densitometric method was used for the determination of drugs under investigation. The identification of degradation products was carried out by using 1H NMR. The degradation processes that occurred in drugs under investigation are described with kinetic parameters (k, t0.1, and t0.5) and energy of activation (Ea). It has been found that the stability of drugs increases toward lipophilic propranolol in the assumed experimental model. The rate constants k decrease, contrary to t0.1, t0.5, and Ea, which vary comparably to logP, thus increasing from the most hydrophilic atenolol, through acebutolol, of lower polarity, to the most lipophilic propranolol. This study demonstrated that the stability of chosen beta-adrenergic blocking agents increases with their lipophilicity.
本研究的主要目的是研究用logP描述的阿替洛尔、醋丁洛尔和普萘洛尔的极性与表征它们在酸性溶液中降解过程的动力学和热力学参数之间的关系。水解在盐酸中于0.1 mol/L、0.5 mol/L和1 mol/L的质量摩尔浓度下，在40℃、60℃和90℃进行2小时。采用色谱 - 光密度法测定所研究的药物。通过1H NMR对降解产物进行鉴定。用动力学参数（k、t0.1和t0.5）和活化能（Ea）描述所研究药物中发生的降解过程。发现在假定的实验模型中，药物稳定性向亲脂性的普萘洛尔增加。速率常数k减小，与t0.1、t0.5和Ea相反，它们与logP的变化相当，因此从亲水性最强的阿替洛尔，经过极性较低的醋丁洛尔，到亲脂性最强的普萘洛尔依次增加。本研究表明，所选β - 肾上腺素能阻滞剂的稳定性随其亲脂性增加。
