Active drug substance impurity profiling part I. LC/UV diode array spectral matching.

Monitoring of drug substance impurities is routinely accomplished using HPLC. However, HPLC retention times can vary, resulting in uncertainty as to whether a peak at a new retention time is a new impurity. Because standards of the minor impurities (less than 0.1% by area) are not usually available, some method is needed to characterize each of these peaks without isolating them. This on-line characterization might be accomplished using UV diode array spectral matching. This work sought to assess the sensitivity and selectivity of UV spectral matching for monitoring the impurity profile of drugs, using as an illustration DuP 941, an anti-cancer drug under development. An ultraviolet spectral data library was generated for a number of the DuP 941 impurities in the earliest safety lot. Impurities in several subsequent lots of DuP 941 were then examined to see how well their spectral characteristics matched those of the spectra contained in the library. We found LC/UV spectral matching to be a powerful method to monitor Dup 941 impurities even down to levels well below 0.1% by area. Critical factors that were shown to influence the utility of the technique include detector sensitivity, lamp intensity, and the presence of other impurities with very similar UV spectra.