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.
J Chromatogr B Analyt Technol Biomed Life Sci
; 768(2): 231-7, 2002 Mar 05.
Article
en En
| MEDLINE
| ID: mdl-11888050
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Pirazoles
/
Cromatografía Líquida de Alta Presión
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Chromatogr B Analyt Technol Biomed Life Sci
Asunto de la revista:
ENGENHARIA BIOMEDICA
Año:
2002
Tipo del documento:
Article
País de afiliación:
Japón