Quantitation of the antitumour 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 muBondapak 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 less than 10%) was 10 nM. The method was sufficiently sensitive to allow pharmacokinetic analyses of 30 mumol/kg doses for more than six half-lives (t1/2) in rabbits (t1/2 = 4) and mice (t1/2 = 1.3 h).
Young
D
D
Department of Pharmacology and Clinical Pharmacology, University of Auckland School of Medicine, New Zealand.
Evans
P C
PC
Paxton
J W
JW
D000166:Acridines; D000609:Aminoacridines / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D051379:Mice; D011817:Rabbits; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence
D000166:Acridines; D000609:Aminoacridines; D000970:Antineoplastic Agents; C058332:N-(2'-(dimethylamino)ethyl)acridine-4-carboxamide