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

Examination of the stability of clonazepam, diazepam, alprazolam, haloperidol, and doxepin in basic solutions was performed, together with an assessment of the kinetic (k, t0.1i t0.5) and thermodynamic (Ea, ΔH++i ΔS++) stability-indicating parameters, which were compared with the lipophilicity (log P) of the studied drugs. It was observed that the calculated values of Ea, ΔH++ and ΔS++ 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.

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