title: Determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin in human plasma by sensitive high-performance liquid chromatography with fluorescence detection.
abstract: Two sensitive reversed-phase high-performance liquid chromatographic fluorescence methods, with simple sample handling at the site of the patient, are described for the determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin (9AC). For 9AC lactone, the sample preparation was a liquid-liquid extraction with acetonitrile-n-butyl chloride (1:4, v/v), whereas the sample preparation for 9AC total (lactone plus carboxylate) was a simple deproteinization with 5% perchloric acid-methanol (1:1, v/v), which results in the conversion of the carboxylate into the lactone form. The lower limits of quantitation were 50 pg/ml and 100 pg/ml for 9AC lactone and 9AC total, respectively. The within-run precisions at four tested concentrations were < or = 6.3% for 9AC lactone and < or = 5.3% for 9AC total. The between-run precisions were < or = 8.9% and < or = 5.6%, respectively. The assays were developed to enable pharmacological analysis of 9AC in a bioavailability and oral phase I study in patients with solid tumors.
authors.affiliation: Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek) and University Hospital Rotterdam, Netherlands.
authors.forename: W J
authors.initials: WJ
authors.lastname: Loos
authors.forename: A
authors.initials: A
authors.lastname: Sparreboom
authors.forename: J
authors.initials: J
authors.lastname: Verweij
authors.forename: K
authors.initials: K
authors.lastname: Nooter
authors.forename: G
authors.initials: G
authors.lastname: Stoter
authors.forename: J H
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood* / Q000737:chemistry / Q000627:therapeutic use; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000627:therapeutic use; D002264:Carboxylic Acids / Q000097:blood* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007783:Lactones / Q000097:blood* / Q000737:chemistry; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D007783:Lactones; C080125:9-aminocamptothecin; D002166:Camptothecin