Pharmacokinetics of A New Antitumor Agent, 1-(3-(Furo(3,2-C)quinolin-4-ylamino)phenyl)-ethanoe -O-methyl-oxime, in Rat Using A High Performance Liquid Chromatography Method

Furo(3,2-C)quinolin-4-ylamino)phenyl)ethanoe-O-methyl-oxime (CCK3) is an antitumor agent, particularly active against the growth of the renal cancer cell, UO-31, and two melanoma cancer cells, UACC-257 and UACC-62, as indicated in the NCI's full panel of 60 human cancer cell lines cytotoxicity evaluation. From the structure-activity relationships between amsacrine and CCK3, C CK3 was expected to have longer half-life than amsacrine in plasma. Therefore, a reversed-phase high performance liquid chromatogr aphy method was developed and validated for the determination of pharmacokinetics of CCK3 in rats. The plasma samples were spiked w ith the internal standard 2-naphthol and extracted using dichloromethane. A C18 column (55 × 4 mm) was used for the separation of analytes with a mobile phase consisted of 30% acetonitrile, 5% tetrahydrofuran and 65% pH 3.0 of McIlvaine buffer at a flow rat e of 1.0 mL/min. CCK3 was detected and utilized by electrochemical detector at 1.0 voltage and 10 nA. Intra- and inter-day precisi on and accuracy were acceptable down to the limit of quantitation of 10 ng/mL. The lower limit of detection was 5 ng/mL. As for the in vivo study, the pharmacokinetic parameters of CCK3 in rats after intravenous administration of 3.97 and 7.94 mg/kg were determined. The apparent volume of distribution, half-life and clearance showed no significant difference between these two dosages. The area under the plasma concentration time curve increased proportionally with increase in dose. The half-life of CCK3 was prolonged 3 fold s, compared to amsacrine. Therefore, CCK3 might have the potential to be tested clinically.