Simultaneous determination of a novel anticancer drug, TAS-103, and its N-demethylated metabolite in monkey plasma by high-performance liquid chromatography using solid-phase extraction

• Published in: Journal of chromatography. B, Biomedical sciences and applications Vol. 691; no. 1; pp. 179 - 185
• Main Authors: Azuma, Ryotaro, Urakawa, Akira
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 28.03.1997; Elsevier Science
• Subjects: 6-{[2-(Dimethylamino)ethyl]amino}-3-hydroxy-7 H-indeno[2,1- c]quinolin-7-one dihydrochloride; Aminoquinolines - blood; Aminoquinolines - pharmacokinetics; Analysis; Animals; Antineoplastic Agents - blood; Biological and medical sciences; Chromatography, High Pressure Liquid - methods; Demethyl-TAS-103; Drug Stability; General pharmacology; Hydrogen-Ion Concentration; Indenes - blood; Indenes - pharmacokinetics; Macaca fascicularis; Male; Medical sciences; Pharmacology. Drug treatments; Reproducibility of Results; Sensitivity and Specificity; TAS-103; TAS-103; 6-{[2-(Dimethylamino)ethyl]amino}-3-hydroxy-7 H-indeno[2,1- c]quinolin-7-one dihydrochloride; Demethyl-TAS-103; Antineoplastic agent; Biological fluid; Solid phase extraction; Intravenous administration; Metabolite; Monkey; HPLC chromatography; Quinoline derivatives; Visible spectrometry; Blood plasma; Vertebrata; Mammalia; Analysis method; Animal; Simultaneous measurement; Primates; Pharmacokinetics; Quantitative analysis
• ISSN: 0378-4347; 1387-2273
• DOI: 10.1016/S0378-4347(96)00449-5

A simple and rapid method for the analysis of a novel anticancer drug, TAS-103, and its metabolite demethyl-TAS-103 in monkey plasma has been developed. This method is based on high-performance liquid chromatography with visible detection at 460 nm after solid-phase extraction with a Sep-Pak Vac PS-2 cartridge. The extraction recoveries of each compound, including the internal standard TAS-1-018, were from 88 to 102%. The quantitation limit of each compound was 5.0 ng/ml in 0.5 ml of plasma. The coefficients of variation for each compound ranged from 0.9 to 4.9%, and relative errors for each compound ranged from −3.8 to 4.6%. Both compounds in monkey plasma were stable at −80°C for 39 days and the extracts were stable at ambient temperature for 24 h. This method has been demonstrated to be useful for the pharmacokinetic study of TAS-103 in monkey plasma after intravenous administration.