Dependence of the kinetic and thermodynamic parameters on hydrophilic-lipophilic character of alprazolam, clonazepam, diazepam, doxepin and haloperidol in alkaline environment

作者：Maslanka Anna^*; Krzek Jan; Szlosarczyk Marek; Zmudzki Pawel; Wach Katarzyna

来源：International Journal of Pharmaceutics, 2013, 455(1-2): 104-112.

DOI：10.1016/j.ijpharm.2013.07.050

• Stability studies
• Lipophilicity
• TLC
• LC/MS

Examination of the stability of clonazepam, diazepam, alprazolam, haloperidol, and doxepin in basic solutions was performed, together with an assessment of the kinetic (k, t(0.1) i t(0.5)) and thermodynamic (E-a, Delta H** i Delta S**) stability-indicating parameters, which were compared with the lipophilicity (log P) of the studied drugs. It was observed that the calculated values of E-a, Delta H** and Delta S** for the studied drugs increased from 41.04 kJ/mol to 125.50 kJ/mol, from 37.82 kJ/mol to 122.24 kJ/mol and from -167.09 J/Kmol to 53.02 J/Kmol, respectively, along with an increase of lipophilicity (log P) from 2.12 to 4.30 for the most hydrophilic alprazolam to the most lipophilic haloperidol. The degradation products were identified using UPLC/MS/MS method.

• 出版日期2013-10-15