The detection of multiple closely eluting compounds in a HPLC analysis of a complex multicomponent system was performed by the application of the simple-to-use interactive self-modelling mixture analysis approach (SIMPLISMA), the orthogonal projection approach (OPA) and Needle Search (NS). None of these three approaches succeeded completely when they were applied on the whole data matrix. The OPA and NS methods were slightly modified and applied on smaller parts of the data set. In this way the local complexity of the unresolved mixtures become more favourable which increases the sensitivity of both methods.