Characterization of acid–base properties of unstable drugs using a continuous-flow system with UV–vis spectrophotometric detection

In this paper, we propose a continuous-flow system for the study of the acid–base characteristics of unstable drugs. 5-Azacytidine has been selected as a first model of unstable compound, which progressively decomposes in aqueous solutions. Besides, other compounds undergoing hydrolysis and oxidation side reactions have been also analyzed to explore the performance of the method. In comparison with conventional batch titrations, the drug decomposition can be minimized by the continuous renewal of the analyte solution. The composition of the buffer mixture is varied on-line during the process from successive changes in the flow rates of acid and basic stock solutions. As a result, the pH value of the test solution is varied in a controlled manner in the range of 1–13. Multivariate curve resolution based on alternating least squares has been used to extract relevant information concerning the acid–base properties of analytes. Results from the continuous-flow system have been compared with those obtained, using batch spectrophotometric titrations, and in the case of fast degradations, the performance of the proposed procedure has been superior.