Determination of 9-nitrocamptothecin and its metabolite 9-aminocamptothecin in human plasma using high-performance liquid chromatography with ultraviolet and fluorescence detection.
A high-performance liquid chromatography assay is described for the determination of the investigational anti-cancer drug 9-nitrocamptothecin (9-NC) and its metabolite 9-aminocamptothecin (9-AC) as the total of their lactone and carboxylate forms. The sample pre-treatment consisted of a deproteinisation step and a quantitative acid-catalyzed conversion of all 9-NC and 9-AC into their lactone forms and a subsequent solid-phase extraction. Redissolved extracts were analyzed on a Prodigy analytical column, using a mixture of methanol-phosphate buffer (pH 2.5). Detection was concomitantly performed with UV for 9-NC and fluorimetrically for 9-AC. The lower limit of quantifications were 10 ng/ml and 2.5 ng/ml for the determination of 9-NC and 9-AC, respectively, using 500 microl of plasma. The presented method was successfully applied to a clinical pharmacokinetic study.
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands. apnsc@slz.nl
Nadja E
NE
Schoemaker
Hilde
H
Rosing
Sindy
S
Jansen
Patrick
P
Schöffski
Jinee
J
Rizzo
Jan H M
JH
Schellens
Jos H
JH
Beijnen
D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence / Q000379:methods*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*
C080125:9-aminocamptothecin; C079905:rubitecan; D002166:Camptothecin