2.When authentic samples of impurities are not available. A stressed drug

product can be analyzed to show separation of the most significant related

substances. In addition, the peak homogeneity of the stressed sample should

be investigated by PDA or mass spectrometry. Alternatively, one may use

an orthogonal procedure to verify the method specificity. The orthogonal

method can be a different technique (e.g., capillary electrophoresis, thin-

layer chromatography) or different type of HPLC analysis (e.g., reversed

phase versus normal phase). For example, compare the related substance

profile in the original HPLC method and that of the orthogonal method. To

demonstrate method specificity, the significant related substances should be

consistent in these methods.