Rapid liquid-chromatographic determination of metformin in plasma and urine

We describe an analysis for metformin in plasma and urine by use of cation-exchange "high-performance" liquid chromatography. The assay requires only 0.5 mL of sample and involves pretreatment with trichloroacetic acid containing an internal standard (1-propylbiguanide), followed by centrifugation and injection into the chromatograph. The column eluent is monitored at 230 nm. Metformin and 1-propylbiguanide give retention times of 8 and 10 min, respectively. Within-day and between-day precision (CV) for the assay of plasma containing 2 mg (1.2 X 10(-5) mol) of metformin hydrochloride per liter was 3.6 and 3.9%, respectively. Similar precision was obtained for urine. The limit of detection is about 0.1 mg (6.0 X 10(-7) mol) of metformin hydrochloride per liter. Several commonly used drugs, including other oral hypoglycemic agents, do not interfere with this method.