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.

Mixed‐mode SPE for a multi‐residue analysis of benzodiazepines in whole blood using rapid GC with negative‐ion chemical ionization MS

“…The hydrolytic degradation of benzodiazepines was observed at 25.0 ± 0.1°C in very acidic solution (1.0 M HCl at pH 0) where after 2 h, the ring of diazepine is practically opened. In less acidic solutions (0.001, 0.01, and 0.1 M) the ring‐opening reaction lasted for up to 4 h until hydrolysis equilibrium was reached .…”

Development and validation of high-performance liquid chromatographic methods for the determination of 14-benzodiazepines in bio-fluids

“…The hydrolysis processes have been studied by several authors and the resulting benzophenones have been used for the detection and determination of 1,4-benzodiazepines (34,35,36,37,38). The main disadvantage of analysis of the benzodiazepines through their benzophenones is that hydrolysis of different benzodiazepines can produce the same benzophenone, with the corresponding lack of selectivity.…”

“…shown by quantitative study of an acid hydrolysis (t = 25°C). Four species were simultaneously present in solution when equilibrium was established; their equilibrium constants were calculated by Damjanović et al (36).…”