Study of acid hydrolysis of bromazepam

Abstract

Quantitative study of an acid hydrolysis of bromazepam, which in acidic solution simultaneously undergoes reversible 4,5-azomethine bond cleavage and protolytic reactions, was performed (t = 25 °C). When an equilibrium is established, four species are simultaneously present in solution. Two approaches, both based on theoretically derived dependence between the absorbance (A) and the solution acidity ([H3O+]), were used to determine appropriate equilibrium constants. In the first, the least-squares method was used to fit experimentally obtained (A, [H3O+]) value pairs to a derived function. With values obtained as fitting parameters, the probability distribution for equilibrium constants was calculated with the virtual experiments performed using Monte Carlo simulations. In the second one, spectrophotometric analysis indicated an existence of two distinct pH intervals, both with three dominant species involved. Spectral data were used to calculate equilibrium constants by a linear curve fitting analysis. Values obtained for equilibrium constants from the numerical and the experimental approaches are in good accordance and were used to calculate distribution of all the species as a function of pcH. Key words: bromazepam, acid hydrolysis, equilibrium constants.