Chemical stability studies of solutions

This capability for measuring chemical degradation over relatively short observation periods may prove to be an extremely powerful analytical technique that could greatly support conventional chemical stability studies or in some cases replace them altogether. The use of isothermal microcalorimetry in the study of chemical stability in the solution phase is relatively straightforward. The sample is placed in the reaction ampoule and measurements are made. However the difficulty arises in interpretation of the data and, in particular, with reaction kinetics. This is reflected in the literature where attempts to analyse reaction kinetics are normally reserved for first order reactions that are relatively easy to solve. However, there are some promising methods for data analysis which may be divided into three categories. The choice of method depends on the information required from the study. 

The first method is a simple approach where an observation of a calorimetric signal that is not at the baseline is indicative of a chemical reaction. Reactions in the solution phase are not complicated by morphological changes. However, care should be taken that the observed calorimetric signal is for a chemical reaction and not a physical change, such as precipitation. This non-quantitative method of analysis is useful as a screen for potentially unstable compounds. 

The second approach is slightly more useful in that a quantitative analysis can be made if the reaction rate is sufficiently fast so that the observation period captures a significant proportion of the overall reaction. The progress of a reaction can be determined by the ratio of area under the calorimetric curve at any time to the area at infinite time. 

The final method is a sophisticated analysis of the data that allows the calculation of the kinetic, thermodynamic and mechanistic parameters to 

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