HPLC MICROMETHOD FOR AMRINONE AND METABOLITES IN PATIENTS RECEIVING CONCURRENT CEPHALOSPORIN THERAPY

Amrinone (AMR), a bipyridine derivative, is receiving increasing use i n postoperative cardiac patients as an inotrope and vasodilator. The h emodynamic response to amrinone in adults is linearly related to AMR c oncentrations, warranting therapeutic drug monitoring. We report a rap id microsample HPLC method for monitoring AMR and its principal metabo lites, N-acetyl (N-ac) and N-glycolyl (N-gly) AMR. Serum was precipita ted with acetonitrile, and the supernatant fluid was then injected int o a C-18 narrow-bore column. The mobile phase consisted of a 0.1 mol/L sodium phosphate buffer (pH 6) with a,gradient of acetonitrile going from 50 to 100 mL/L of eluent. Detection with a diode-array detector ( DAD) concurrently monitored the absorbances at 320 and 345 nm. Monitor ing 320 nm allows optimal quantification of AMR, N-gly, and N-ac. Pati ents often receive concurrent cephalosporin therapy, which is detectab le at 320 nm but not 345 nm. Because cephalosporins coelute with AMR o r metabolites, monitoring at 345 nn allows separation of these antibio tics from AMR and metabolites while retaining a detection limit of 0.5 mg/L.