title: High-performance liquid chromatographic analysis for the determination of a novel polymer-bound camptothecin derivative (MAG-camptothecin) and free camptothecin in human plasma.
abstract: A selective HPLC assay is described for the determination of free and total (free plus polymer-bound) camptothecin (CPT) in human plasma after administration of the anti-tumor drug MAG-CPT (polymer bound camptothecin). Total CPT levels were determined after hydrolysis and free CPT was extracted from acidified plasma using Oasis solid-phase extraction material. Extracts were analyzed on a Zorbax SB-C8 analytical column, using a mixture of acetonitrile-25 mM phosphate buffer (pH 4.0) as the eluent. Detection was performed fluorimetrically. Concentrations of polymer-bound CPT were calculated by subtraction of free from total CPT. The lower limits of quantitation of the methods were 100 ng/ml for total and 1.0 ng/ml for free CPT using 50 microl and 250 microl plasma, respectively. Special attention was paid to the stability of the analytes. The presented method was successfully applied in a clinical pharmacokinetic study in our institute.
authors.affiliation: Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam. apnsc@slz.nl
authors.forename: N E
authors.initials: NE
authors.lastname: Schoemaker
authors.forename: E
authors.initials: E
authors.lastname: Frigerio
authors.forename: D
authors.initials: D
authors.lastname: Fraier
authors.forename: J H
authors.initials: JH
authors.lastname: Schellens
authors.forename: H
authors.initials: H
authors.lastname: Rosing
authors.forename: S
authors.initials: S
authors.lastname: Jansen
authors.forename: J H
authors.initials: JH
authors.lastname: Beijnen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002138:Calibration; D002166:Camptothecin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D011108:Polymers; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D002166:Camptothecin