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Article Title

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

Abstract

1-[3-(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, CCK3 was expected to have longer half-life than amsacrine in plasma. Therefore, a reversed-phase high performance liquid chromatography method was developed and validated for the determination of pharmacokinetics of CCK3 in rats. The plasma samples were spiked with 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 rate of 1.0 mL/min. CCK3 was detected and utilized by electrochemical detector at 1.0 voltage and 10 nA. Intra- and inter-day precision 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 folds, compared to amsacrine. Therefore, CCK3 might have the potential to be tested clinically.

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