Sensitive isocratic high-performance liquid chromatographic determination of a novel indoloquinone cytotoxic drug (EO9) in human plasma and urine.
A reversed-phase isocratic high-performance liquid chromatographic method is described for the simultaneous determination of EO9, 3-hydroxymethyl-5-aziridinyl-1-methyl-2-(1H-indole-4,7-dione)prop-beta- en-alpha-ol (I), and its ring-opened aziridine analogue EO5A (II), employing ultraviolet detection. Solid-phase sample extraction was used without addition of an internal standard. Plots of peak heights and areas of I and II were linear in the range 5-10,000 ng/ml. The lower limit of detection of both I and II in plasma was 2 ng/ml. The between-day variation of I was 13.9% at 5 ng/ml and lower than 6.2% for concentrations > or = 10 ng/ml. The between-day variation of II at 5 ng/ml was 13.8% and lower than 4.5% for concentrations > or = 10 ng/ml. The assay was developed to enable pharmacological guiding of a phase I study of I in solid tumour cancer patients.
Schellens
J H
JH
Department of Medical Oncology, Rotterdam Cancer Institute, Netherlands.
Loos
W
W
Beijnen
J H
JH
Stoter
G
G
Verweij
J
J
D000970:Antineoplastic Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D001388:Aziridines / Q000032:analysis* / Q000097:blood / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007202:Indicators and Reagents; D045563:Indolequinones; D007211:Indoles / Q000032:analysis* / Q000097:blood / Q000652:urine; D013056:Spectrophotometry, Ultraviolet
D000970:Antineoplastic Agents; D001388:Aziridines; D007202:Indicators and Reagents; D045563:Indolequinones; D007211:Indoles; C082259:EO 5A; C060817:apaziquone