Analytical Methods for Photostability Testing

The requirements for the analytical methods acceptable for photostability testing are increased because the methods have to be more selective, i.e., more indicative of stability. The method must permit the separation, detection, and quantification of all degradation products at very low levels. For unknown impurities, the analytical method must provide as much qualitative information as possible. The following sections give an overview of current analytical techniques used in conjunction with a photostability testing program. Several examples of their application, from our own photostability studies, will also be presented. 

A major drawback of the spectrophotometric analysis is the fact that many photodegradation reactions provoke no or only negligible spectral changes. This leads to the fact that many photoreactions cannot be registered accordingly. 

The irradiation of a solution of ketoconazole will illustrate that situation The monitoring of the absorption at the spectral maximum of ketoconazole at 242 nm only gives a decrease of 9% after an irradiation period of 100 minutes (Fig. 4A). A comparison of the complete UV absorption spectrum before and after 100 minutes irradiation shows more significant changes in the range around 300 nm (Fig. 4B). But the real extent of decomposition only became apparent with the results of the HPLC stability assay. The HPLC analysis proved that already after 5 minutes 50% of the drug was decomposed by photolysis. 

This example clearly demonstrates that the spectrophotometric analyses are not always suitable for stability measurements. Small changes in the photostability of the sample are not always evident. Analysis using more selective and sensitive chromatographic, stability-indicating techniques give a true picture of the course of events. 

---