For the development of selective HPLC methods to be used for quantitative determination of impurities, degradants, excipients and active in the drug substance as well as in the drug product a screening concept is currently used. The concept is based on a matrix screening between different pH [2.5, 4.8, 7, 9] and stationary phases [Zorbax Extend C18, Bonus RP; Waters XTerra MS C18, XTerra RP18, XTerra Phenyl, SymmetryShield]. The screening module consists of 4 HPLC systems each operating with a different MS compatible mobile phase at a different pH. Each HPLC system is connected with a valve switcher to permit automated selection between 8 columns with different selectivity. After screening, 32 chromatograms for each sample have to be evaluated. The best separation is selected based on pH and column selectivity.