ACTIVE-DRUG SUBSTANCE IMPURITY PROFILING - PART-I - LC UV DIODE-ARRAYSPECTRAL MATCHING/

Monitoring of drug substance impurities is routinely accomplished usin g HPLC. However, HPLC retention times can vary, resulting in uncertain ty as to whether a peak at a new retention time is a new impurity. Bec ause standards of the minor impurities (less than 0.1% by area) are no t usually available, some method is needed to characterize each of the se peaks without isolating them. This on-line characterization might b e accomplished using UV diode array spectral matching. This work sough t to assess the sensitivity and selectivity of UV spectral matching fo r monitoring the impurity profile of drugs, using as an illustration D uP 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 impuritie s even down to levels well below 0.1% by area. Critical factors that w ere shown to influence the utility of the technique include detector s ensitivity, lamp intensity, and the presence of other impurities with very similar UV spectra. (C) 1998 Elsevier Science B.V.