High-performance liquid chromatographic analysis of lactone and hydroxy acid of new antitumor drug, DX-8951 (Exatecan), in mouse plasma

A sensitive high-performance liquid chromatographic (HPLC) method has been developed and validated for the determination of lactone and total drug (la ctone plus hydroxy-acid) of DX-8951 in mouse plasma. Solid-phase extraction by C18 cartridge separated lactone from total drug of DX-8951, Analysis wa s performed using a reverse-phase ODS column with a mobile phase consisting of acetonitrile/0.05 M potassium dihydrogen phosphate (pH 3) (18:82, v/v) at a flow rate of 1 ml/min. The limits of quantitation of lactone and total drug were 3 ng/ml in plasma and a linear range of determination were obser ved over the concentration of 3 to 500 ng/ml. This method was applied to ph armacokinetic study in male mice treated with a single intravenous administ ration of either lactone or hydroxy-acid of DX-8951. The plasma concentrati ons of lactone from 2 to 6 h after, dosing were similar regardless of the f orm of DX-8951 administered.