Metformin is a biguanide-based anti-diabetic drug. It is a very polar organic compound that has no retention on reversed-phase column unless an ion-pairing reagent is employed. Metformin was retained on a Primesep 200 column based on cation-exchange mechanism. Method can be used for analysis of metformin and related substances in pharmaceutical formulations. Due to low UV activity a more UV-transparent mobile phase is required. Metformin can be also monitored by ELSD and LC/MS with corresponding mobile phase (TFA, ammonium formate or ammonium acetate).