title: Determination of total and lactone form of a new camptothecin derivative gimatecan (ST1481) and its metabolite ST1698 in human plasma by high-performance liquid chromatography with fluorimetric detection.
abstract: A new sensitive high-performance liquid chromatographic (HPLC) method for the determination of gimatecan (ST1481), a new camptothecin derivative, and its metabolite (ST1698) in plasma sample has been developed. The method consisted of on-line column solid phase extraction of analytes from human plasma, chromatographic separation by isocratic elution, then fluorimetric detection. The limits of quantitation were 0.25 ng/mL for both the analytes. The recovery of the extraction procedure was in the range of 62.8-71.1% for all the compounds. Good linearity (R(2)>0.999) was observed within the calibration ranges studied: 0.25-25 ng/mL for both ST1481 and ST1698. Precision was in the range 1.2-4.3%, and accuracy was always lower than 4.7%. Surprisingly, after administration of ST1481 to humans, plasma concentrations found were higher than expected, while metabolite plasma concentrations were negligible. For this reason, a second calibration curve range was validated to quantify ST1481 in human plasma, ranging from 5 to 200 ng/mL. A good accuracy and precision were obtained, confirming the usefulness of the procedure. By using neutral analytical condition the intact lactone form was estimated in plasma samples from a patient. The lactone form amounted to 80-100% of the total ST1481.
authors: Research and Development Division, Department of Pharmacokinetics and Metabolism, sigma-tau Industrie Farmaceutiche Riunite, via Pontina Km 30,400, 00040 Pomezia, Rome, Italy.
authors: Silvia
authors: S
authors: Pace
authors: Francesca
authors: F
authors: Capocasa
authors: Carlo
authors: C
authors: Tallarico
authors: Roberta
authors: R
authors: Frapolli
authors: Massimo
authors: M
authors: Zucchetti
authors: Antonio
authors: A
authors: Longo
mesh_terms: D000970:Antineoplastic Agents / Q000097:blood / Q000378:metabolism; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D017321:Clinical Trials, Phase I as Topic; D004791:Enzyme Inhibitors / Q000097:blood* / Q000378:metabolism; D006801:Humans; D015203:Reproducibility of Results
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C433984:ST 1481; C544699:ST 1698; D002166:Camptothecin