High-performance liquid chromatographic analysis for the determination of a novel polymer-bound camptothecin derivative (MAG-camptothecin) and free camptothecin in human plasma.
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.
Schoemaker
N E
NE
Department of Medical Oncology, Antoni van Leeuwenhoek Hospital/The Netherlands Cancer Institute, Amsterdam. apnsc@slz.nl
Frigerio
E
E
Fraier
D
D
Schellens
J H
JH
Rosing
H
H
Jansen
S
S
Beijnen
J H
JH
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
D000972:Antineoplastic Agents, Phytogenic; D011108:Polymers; D002166:Camptothecin