title: Determination of the anticancer drug KW-2170, a pyrazoloacridone derivative, and its metabolites in human and dog plasma by high-performance liquid chromatography using an electrochemical detector.
abstract: KW-2170, 5-(3-aminopropyl) amino-7,10-dihydroxy-2-(2-hydroxethyl)-aminoethyl-6H-pyrazolo [4,5,1-de] acridin-6-one dihydroxychloride, is a novel anticancer agent under clinical development. We have established a highly sensitive method which can simultaneously quantitate KW-2170 and its two metabolites, a carboxylic (M1) and hydroxylated (M2) derivative involving the 5-position, in human and dog plasma. KW-2170 and its metabolites were extracted from plasma using a weak cation-exchange cartridge and then determined by HPLC using an electrochemical detector (ED). Over the concentration range 0.1-50 ng/ml, precision and accuracy of intra- and inter-day assay were within 11% in human plasma. In dog plasma, they were within 17% at the lower quantitation limit and within 11% at other concentrations. These three compounds were stable during the assay procedure, freeze-thawing cycles and during long-term storage. Using this methodology, the pharmacokinetics of KW-2170 in a dog could be monitored over 24 h. This method is suitable for evaluation of the detailed pharmacokinetics of KW-2170 and its metabolites in humans and dogs.
authors.affiliation: Pharmaceutical Research Institute, Kyowa Hakko Kogyo, Shizuoka, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kuramitsu
authors.forename: Katsumi
authors.initials: K
authors.lastname: Takai
authors.forename: Rui
authors.initials: R
authors.lastname: Ohashi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kuwabara
mesh_terms: D000166:Acridines / Q000493:pharmacokinetics; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood* / Q000493:pharmacokinetics; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D004563:Electrochemistry; D006801:Humans; D011720:Pyrazoles / Q000097:blood* / Q000493:pharmacokinetics; D015203:Reproducibility of Results
chemical_list: D000166:Acridines; D000970:Antineoplastic Agents; D011720:Pyrazoles; C113299:KW 2170