QUANTITATION OF THE ANTITUMOR AGENT N-[2-(DIMETHYLAMINO)ETHYL]ACRIDINE-4-CARBOXAMIDE IN PLASMA BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

N-[2-(Dimethylamino)ethyl]acridine-4-carboxamide is a new experimental antitumour agent which has excellent in vivo activity against the Lewis lung tumour in mice. A reversed-phase high-performance liquid chromatographic method is described for the measurement of this agent in plasma. The internal standard was N-[2-(diethylamino)ethyl]acridine-4-carboxamide. The compounds of interest were extracted from plasma (0.2 ml) with acetonitrile and further purified on C18 solid-phase extraction Bond Elut columns. After elution with acetonitrile-ammonium acetate buffer and evaporation, the final separation was carried out on a C18 μBondapak column with fluorimetric detection. Over the plasma concentration range 100-5000 nM, the intra- and inter-assay coefficients of variation were less than 4.1 and 7.7%, respectively. The accuracy of the method varied from 97 to 105% of the theoretical values. The lowest concentration which could be measured with acceptable accuracy (±10%) and precision (coefficient of variation < 10%) was 10 nM. The method was sufficiently sensitive to allow pharmacokinetic analyses of 30 μmol/kg doses for more than six half-lives (t 1 2 in rabbits (t 1 2 = 4 min) and mice (t 1 2 = 1.3 h). © 1990.