Obelisc R column can be successfully used for analysis of hydrophobic and hydrophilic basic and acidic drugs and corresponding counter-ions. This approach can be used for analysis of various cold and cough composition, pain killers, and other prescription and over-the-counter medications. Within pH 3-5, both cation- and anion mechanism are present on the column, along with hydrophobic interaction. Selectivity of this mixed-mode separation is controlled by the amount of acetonitrile, buffer concentration and buffer pH. Method is robust and reproducible, and can be used as a common HPLC method for analysis of drug molecules and compositions.